Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages.
AuthorsBenten WP,Lieberherr M,Stamm O,Wrehlke C,Guo Z,Wunderlich F
JournalMolecular biology of the cell
PubMed ID10512854
Testosterone acts on cells through intracellular transcription-regulating androgen receptors (ARs). Here, we show that mouse IC-21 macrophages lack the classical AR yet exhibit specific nongenomic responses to testosterone. These manifest themselves as testosterone-induced rapid increase in intracellular free [Ca(2+)], which is due to release of Ca(2+) from intracellular Ca(2+) stores. ... More
Authors
Journal
PubMed ID9030618
Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups.
AuthorsEkkapongpisit M, Giovia A, Follo C, Caputo G, Isidoro C,
JournalInt J Nanomedicine
PubMed ID22904626
Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10-30 nm versus 50 nm), type of material (mesoporous silica ... More
Induction of autophagy and cell death by tamoxifen in cultured retinal pigment epithelial and photoreceptor cells.
AuthorsCho KS, Yoon YH, Choi JA, Lee SJ, Koh JY,
JournalInvest Ophthalmol Vis Sci
PubMed ID22786900
We investigated the mechanism of tamoxifen (TAM) retinotoxicity using human retinal pigment epithelial (RPE)-derived (ARPE-19) and photoreceptor-derived (661W) cells. Cultured ARPE-19 and 661W cells were treated with 5 to 10 µM TAM, and the resultant cell death was quantified using lactate dehydrogenase (LDH) release assay. Cellular oxidative stress was determined ... More
Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.
AuthorsGillard BK, Rosales C, Pillai BK, Lin HY, Courtney HS, Pownall HJ,
JournalBiochemistry
PubMed ID20879789
Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ~400000 HDL particles and ... More
Niemann-Pick C1 functions in regulating lysosomal amine content.
AuthorsKaufmann AM, Krise JP,
JournalJ Biol Chem
PubMed ID18591242
'Mutations in the late endosomal/lysosomal membrane protein Niemann-Pick C1 (NPC1) are known to cause a generalized block in retrograde vesicle-mediated transport, resulting in the hyper-accumulation of multiple lysosomal cargos. An important, yet often overlooked, category of lysosomal cargo includes the vast array of small molecular weight amine-containing molecules that are ... More
Monitoring autophagy in Alzheimer's disease and related neurodegenerative diseases.
AuthorsYang DS, Lee JH, Nixon RA,
JournalMethods Enzymol
PubMed ID19216904
'This chapter describes detailed methods to monitor autophagy in neurodegenerative disorders, especially in Alzheimer''s disease. Strategies to assess the competence of autophagy-related mechanisms in disease states ideally incorporate analyses of human disease and control tissues, which may include brain, fibroblasts, or other peripheral cells, in addition to animal and cell ... More
Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest.
AuthorsFratti RA, Backer JM, Gruenberg J, Corvera S, Deretic V
JournalJ Cell Biol
PubMed ID11489920
'Phagosomal biogenesis is a fundamental biological process of particular significance for the function of phagocytic and antigen-presenting cells. The precise mechanisms governing maturation of phagosomes into phagolysosomes are not completely understood. Here, we applied the property of pathogenic mycobacteria to cause phagosome maturation arrest in infected macrophages as a tool ... More
A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling.
AuthorsDantuma NP, Groothuis TA, Salomons FA, Neefjes J
JournalJ Cell Biol
PubMed ID16606690
'Protein degradation, chromatin remodeling, and membrane trafficking are critically regulated by ubiquitylation. The presence of several coexisting ubiquitin-dependent processes, each of crucial importance to the cell, is remarkable. This brings up questions on how the usage of this versatile regulator is negotiated between the different cellular processes. During proteotoxic stress, ... More
Dynamics and function of phospholipase D and phosphatidic acid during phagocytosis.
AuthorsCorrotte M, Chasserot-Golaz S, Huang P, Du G, Ktistakis NT, Frohman MA, Vitale N, Bader MF, Grant NJ
JournalTraffic
PubMed ID16497229
'Phospholipase D (PLD) produces phosphatidic acid (PA), an established intracellular signalling lipid that has been also implicated in vesicular trafficking, and as such, PLD could play multiple roles during phagocytosis. Using an RNA interference strategy, we show that endogenous PLD1 and PLD2 are necessary for efficient phagocytosis in murine macrophages, ... More
Methods for assessing autophagy and autophagic cell death.
AuthorsTasdemir E, Galluzzi L, Maiuri MC, Criollo A, Vitale I, Hangen E, Modjtahedi N, Kroemer G,
JournalMethods Mol Biol
PubMed ID18425442
'Autophagic (or type 2) cell death is characterized by the massive accumulation of autophagic vacuoles (autophagosomes) in the cytoplasm of cells that lack signs of apoptosis (type 1 cell death). Here we detail and critically assess a series of methods to promote and inhibit autophagy via pharmacological and genetic manipulations. ... More
Two-photon fluorescence absorption and emission spectra of dyes relevant for cell imaging.
AuthorsBestvater F, Spiess E, Stobrawa G, Hacker M, Feurer T, Porwol T, Berchner-Pfannschmidt U, Wotzlaw C, Acker H
JournalJ Microsc
PubMed ID12423261
'Two-photon absorption and emission spectra for fluorophores relevant in cell imaging were measured using a 45 fs Ti:sapphire laser, a continuously tuneable optical parametric amplifier for the excitation range 580-1150 nm and an optical multichannel analyser. The measurements included DNA stains, fluorescent dyes coupled to antibodies as well as organelle ... More
A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment.
AuthorsWunderlich W, Fialka I, Teis D, Alpi A, Pfeifer A, Parton RG, Lottspeich F, Huber LA
JournalJ Cell Biol
PubMed ID11266467
'We have identified a novel, highly conserved protein of 14 kD copurifying with late endosomes/lysosomes on density gradients. The protein, now termed p14, is peripherally associated with the cytoplasmic face of late endosomes/lysosomes in a variety of different cell types.In a two-hybrid screen with p14 as a bait, we identified ... More
Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses.
AuthorsSato K, Yang XL, Yudate T, Chung JS, Wu J, Luby-Phelps K, Kimberly RP, Underhill D, Cruz PD, Ariizumi K
JournalJ Biol Chem
PubMed ID17050534
'Antigen presenting cells recognize pathogens via pattern recognition receptors (PRR), which upon ligation transduce intracellular signals that can induce innate immune responses. Because some C-type lectin-like receptors (e.g. dectin-1 and DCSIGN) were shown to act as PRR for particular microbes, we considered a similar role for dectin-2. Binding assays using ... More
Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin.
AuthorsFiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J
JournalProc Natl Acad Sci U S A
PubMed ID17652175
'We have tested a hypothesis that the natural product curcuminoids, which has epidemiologic and experimental rationale for use in AD, may improve the innate immune system and increase amyloid-beta (Abeta) clearance from the brain of patients with sporadic Alzheimer''s disease (AD). Macrophages of a majority of AD patients do not ... More
Integrin alpha5/beta1 expression mediates HER-2 down-regulation in colon cancer cells.
AuthorsKuwada SK, Kuang J, Li X
JournalJ Biol Chem
PubMed ID15757908
'HER-2 is constitutively activated and overexpressed in many cancers, and its inhibition in colon cancer cells diminishes tumorigenicity and induces apoptosis. Little is known about the regulation of HER-2 signaling in colon cancer cells. Integrin alpha5/beta1 expression is frequently lost in colorectal cancer cells compared with normal intestinal epithelium, and ... More
Quantitative measurement of mast cell degranulation using a novel flow cytometric annexin-V binding assay.
AuthorsDemo SD, Masuda E, Rossi AB, Throndset BT, Gerard AL, Chan EH, Armstrong RJ, Fox BP, Lorens JB, Payan DG, Scheller RH, Fisher JM
JournalCytometry
PubMed ID10404150
'BACKGROUND: Mast cells are primary mediators of allergic inflammation. Antigen-mediated crosslinking of their cell surface immunoglobulin E (IgE) receptors results in degranulation and the release of proinflammatory mediators including histamine, tumor necrosis factor-alpha, and leukotrienes. METHODS: Mast cells were stimulated to degranulate by using either IgE crosslinking or ionophore treatment. ... More
Long-term exposure to CdTe quantum dots causes functional impairments in live cells.
AuthorsCho SJ, Maysinger D, Jain M, Röder B, Hackbarth S, Winnik FM
JournalLangmuir
PubMed ID17279683
'Several studies suggested that the cytotoxic effects of quantum dots (QDs) may be mediated by cadmium ions (Cd2+) released from the QDs cores. The objective of this work was to assess the intracellular Cd2+ concentration in human breast cancer MCF-7 cells treated with cadmium telluride (CdTe) and core/shell cadmium selenide/zinc ... More
Phorbol ester promotes endocytosis by activating a factor involved in endosome fusion.
AuthorsAballay A, Stahl PD, Mayorga LS
JournalJ Cell Sci
PubMed ID10393811
'Previous studies indicate that a zinc- and phorbol ester-binding factor is necessary for in vitro endosome fusion and for the effect of Rab5 on endosome fusion. Rab5 is a small GTPase that regulates membrane fusion between early endosomes derived from either receptor-mediated endocytosis or fluid-phase endocytosis. In its GTP-bound form, ... More
Developmental toxicity of methanol: Pathogenesis in CD-1 and C57BL/6J mice exposed in whole embryo culture.
AuthorsDegitz SJ, Rogers JM, Zucker RM, Hunter ES
JournalBirth Defects Res A Clin Mol Teratol
PubMed ID15108244
'BACKGROUND: Methanol causes axial skeleton and craniofacial defects in both CD-1 and C57BL/6J mice during gastrulation, but C57BL/6J embryos are more severely affected. We evaluated methanol-induced pathogenesis in CD-1 and C57BL/6J embryos exposed during gastrulation in whole embryo culture. METHODS: Conceptuses with five to seven somites were exposed to 0, ... More
Phorbol ester induces elevated oxidative activity and alkalization in a subset of lysosomes.
AuthorsChen CS
JournalBMC Cell Biol
PubMed ID12165102
'BACKGROUND: Lysosomes are acidic organelles that play multiple roles in various cellular oxidative activities such as the oxidative burst during cytotoxic killing. It remains to be determined how lysosomal lumen oxidative activity and pH interact and are regulated. Here, I report the use of fluorescent probes to measure oxidative activity ... More
Helicobacter pylori enter and survive within multivesicular vacuoles of epithelial cells.
AuthorsAmieva MR, Salama NR, Tompkins LS, Falkow S
JournalCell Microbiol
PubMed ID12366404
'Although intracellular Helicobacter pylori have been described in biopsy specimens and in cultured epithelial cells, the fate of these bacteria is unknown. Using differential interference contrast (DIC) video and immunofluorescence microscopy, we document that a proportion of cell-associated H. pylori enter large cytoplasmic vacuoles, where they remain viable and motile ... More
Spontaneous and ligand-induced trafficking of CXC-chemokine receptor 4.
AuthorsTarasova NI, Stauber RH, Michejda CJ
JournalJ Biol Chem
PubMed ID9632631
'A chimeric protein consisting of CXC-chemokine receptor 4 (CXCR4) and the green fluorescent protein (GFP) was used for studying receptor localization and trafficking in real time in stably transduced HeLa, U-937, CEM, and NIH/3T3 cells. CXCR4-GFP was fully active as a co-receptor in mediating human immunodeficiency virus (HIV) entry. Both ... More
Fluorogenic label for biomolecular imaging.
AuthorsLavis LD, Chao TY, Raines RT
JournalACS Chem Biol
PubMed ID17163679
'Traditional small-molecule fluorophores are always fluorescent. This attribute can obscure valuable information in biological experiments. Here, we report on a versatile "latent" fluorophore that overcomes this limitation. At the core of the latent fluorophore is a derivative of rhodamine in which one nitrogen is modified as a urea. That modification ... More
Photoconversion of Lysotracker Red to a green fluorescent molecule.
AuthorsFreundt EC, Czapiga M, Lenardo MJ
JournalCell Res
PubMed ID17893709
'Lysotracker Red DND-99 (is a fluorophore in the form of a conjugated multi-pyrrole ring structure containing a weakly basic amine that selectively accumulates in acidic compartments and exhibits red fluorescence. It is structurally related to Lysotracker Green but has an additional pyrrole ring in conjugation with the primary structure, which ... More
Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.
AuthorsMagez S, Geuskens M, Beschin A, del Favero H, Verschueren H, Lucas R, Pays E, de Baetselier P
JournalJ Cell Biol
PubMed ID9151676
'Trypanosoma brucei is lysed by tumor necrosis factor-alpha (TNF-alpha) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-alpha-gold particles are endocytosed via coated pits and vesicles and are directed towards lysosome-like digestive organelles. The specific uptake ... More
Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles.
AuthorsHu Y, Litwin T, Nagaraja AR, Kwong B, Katz J, Watson N, Irvine DJ,
JournalNano Lett
PubMed ID17887715
'Polycations that absorb protons in response to the acidification of endosomes can theoretically disrupt these vesicles via the "proton sponge" effect. To exploit this mechanism, we created nanoparticles with a segregated core-shell structure for efficient, noncytotoxic intracellular drug delivery. Cross-linked polymer nanoparticles were synthesized with a pH-responsive core and hydrophilic ... More
High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine.
AuthorsFairn GD, Schieber NL, Ariotti N, Murphy S, Kuerschner L, Webb RI, Grinstein S, Parton RG,
JournalJ Cell Biol
PubMed ID21788369
'Phosphatidylserine (PS) plays a central role in cell signaling and in the biosynthesis of other lipids. To date, however, the subcellular distribution and transmembrane topology of this crucial phospholipid remain ill-defined. We transfected cells with a GFP-tagged C2 domain of lactadherin to detect by light and electron microscopy PS exposed ... More
Tetanus toxin is transported in a novel neuronal compartment characterized by a specialized pH regulation.
AuthorsBohnert S, Schiavo G
JournalJ Biol Chem
PubMed ID16236708
'Tetanus toxin binds specifically to motor neurons at the neuromuscular junction. There, it is internalized into vesicular carriers undergoing fast retrograde transport to the spinal cord. Despite the importance of this axonal transport pathway in health and disease, its molecular and biophysical characterization is presently lacking. We sought to fill ... More
AuthorsSteinert S, Lee E, Tresset G, Zhang D, Hortsch R, Wetzel R, Hebbar S, Sundram JR, Kesavapany S, Boschke E, Kraut R,
JournalPLoS ONE
PubMed ID18716682
'BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order ... More
Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells.
'The intracellular activation of trypsinogen, which is both pH- and calcium-dependent, is an important early step in the development of acute pancreatitis. The cellular compartment in which trypsinogen activation occurs currently is unknown. We therefore investigated the site of intracellular trypsinogen activation by using an established cellular model of acute ... More
A role for mitochondria in NLRP3 inflammasome activation.
AuthorsZhou R, Yazdi AS, Menu P, Tschopp J,
JournalNature
PubMed ID21124315
'An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host ''danger'', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we ... More
NAADP controls cross-talk between distinct Ca2+ stores in the heart.
AuthorsMacgregor A, Yamasaki M, Rakovic S, Sanders L, Parkesh R, Churchill GC, Galione A, Terrar DA
JournalJ Biol Chem
PubMed ID17387177
'In cardiac muscle the sarcoplasmic reticulum (SR) plays a key role in the control of contraction, releasing Ca(2+) in response to Ca(2+) influx across the sarcolemma via voltage-gated Ca(2+) channels. Here we report evidence for an additional distinct Ca(2+) store and for actions of nicotinic acid adenine dinucleotide phosphate (NAADP) ... More
Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins.
AuthorsErwig LP, McPhilips KA, Wynes MW, Ivetic A, Ridley AJ, Henson PM
JournalProc Natl Acad Sci U S A
PubMed ID16908865
'Deletion of apoptotic cells from tissues involves their phagocytosis by macrophages, dendritic cells, and tissue cells. Although much attention has been focused on the participating ligands, receptors, and mechanisms of uptake, little is known of the disposition of the ingested cell within the phagosome. Here we show that uptake of ... More
A noninvasive cell-based assay for monitoring proteolytic activity within a specific subcellular compartment.
AuthorsBelkhiri A, Lytvyn V, Guilbault C, Bourget L, Massie B, Nägler DK, Ménard R
JournalAnal Biochem
PubMed ID12123661
'A noninvasive cell-based assay has been developed to monitor the proteolytic activity of cathepsin L within a specific subcellular compartment, the lysosome. The green fluorescent protein (GFP) of Aequorea victoria was selected as a substrate. Targeting to lysosomes was achieved by fusing GFP to preprocathepsin L, which also ensures colocalization ... More
Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis.
AuthorsCao Y, Espinola JA, Fossale E, Massey AC, Cuervo AM, MacDonald ME, Cotman SL
JournalJ Biol Chem
PubMed ID16714284
'Juvenile neuronal ceroid lipofuscinosis is caused by mutation of a novel, endosomal/lysosomal membrane protein encoded by CLN3. The observation that the mitochondrial ATPase subunit c protein accumulates in this disease suggests that autophagy, a pathway that regulates mitochondrial turnover, may be disrupted. To test this hypothesis, we examined the autophagic ... More
Multiphoton confocal microscopy using a femtosecond Cr:forsterite laser.
AuthorsLiu TM, Chu SW, Sun CK, Lin BL, Cheng PC, Johnson I
JournalScanning
PubMed ID11534811
'With its output wavelength covering the infrared penetrating window of most biological tissues at 1,200-1,250 nm, the femtosecond Cr:forsterite laser shows high potential to serve as an excellent excitation source for the multiphoton fluorescence microscope. Its high output power, short optical pulse width, high stability, and low dispersion in fibers ... More
Visualization of G protein-coupled receptor trafficking with the aid of the green fluorescent protein. Endocytosis and recycling of cholecystokinin receptor type A.
AuthorsTarasova NI, Stauber RH, Choi JK, Hudson EA, Czerwinski G, Miller JL, Pavlakis GN, Michejda CJ, Wank SA
JournalJ Biol Chem
PubMed ID9169450
'A chimeric protein consisting of the cholecystokinin receptor type A (CCKAR) and the green fluorescent protein (GFP) was used for studying receptor localization, internalization, and recycling in live cells in real time in four different cell lines. Fusion of the C terminus of the CCKAR to the N terminus of ... More
Lysosomal destabilization in p53-induced apoptosis.
AuthorsYuan XM, Li W, Dalen H, Lotem J, Kama R, Sachs L, Brunk UT
JournalProc Natl Acad Sci U S A
PubMed ID11959917
'The tumor suppressor wild-type p53 can induce apoptosis. M1-t-p53 myeloid leukemic cells have a temperature-sensitive p53 protein that changes its conformation to wild-type p53 after transfer from 37 degrees C to 32 degrees C. We have now found that these cells showed an early lysosomal rupture after transfer to 32 ... More
Verotoxin 1 binding to intestinal crypt epithelial cells results in localization to lysosomes and abrogation of toxicity.
AuthorsHoey DE, Sharp L, Currie C, Lingwood CA, Gally DL, Smith DG,
JournalCell Microbiol
PubMed ID12580945
'Verotoxins (VTs) are important virulence factors of enterohaemorrhagic Escherichia coli (EHEC), a group of bacteria associated with severe disease sequelae in humans. The potent cytotoxic activity of VTs is important in pathogenicity, resulting in the death of cells expressing receptor Gb3 (globotriaosylceramide). EHEC, particularly serotype O157:H7, frequently colonize reservoir hosts ... More
Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in neuronal differentiation.
AuthorsBrailoiu E, Churamani D, Pandey V, Brailoiu GC, Tuluc F, Patel S, Dun NJ
JournalJ Biol Chem
PubMed ID16595650
'Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the cell surface by a multitude of extracellular cues to the regulation of intracellular Ca2+-sensitive targets. Recent studies suggest that agonists differentially select from this molecular palette to generate their characteristic Ca2+ signals but it is still unclear whether different messengers ... More
A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance.
AuthorsPol A, Luetterforst R, Lindsay M, Heino S, Ikonen E, Parton RG
JournalJ Cell Biol
PubMed ID11238460
'Recent studies have indicated a role for caveolin in regulating cholesterol-dependent signaling events. In the present study we have analyzed the role of caveolins in intracellular cholesterol cycling using a dominant negative caveolin mutant. The mutant caveolin protein, cav-3(DGV), specifically associates with the membrane surrounding large lipid droplets. These structures ... More
Insulin-like growth factor I enhances the expression of aromatase P450 by inhibiting autophagy.
AuthorsZhang B, Shozu M, Okada M, Ishikawa H, Kasai T, Murakami K, Nomura K, Harada N, Inoue M,
JournalEndocrinology
PubMed ID20668023
'Aromatase, a key enzyme of estrogen biosynthesis, is transcriptionally regulated by many growth factors. IGF-I enhances aromatase activity in a variety of cells, but the mechanism of action has not been determined. We herein report our finding of a novel mechanism of action for IGF-I. IGF-I enhanced the dexamethasone (DEX)-induced ... More
Disordered calcium crystal handling in antisense CLC-5-treated collecting duct cells.
'Dent''s disease, an X-linked tubulopathy secondary to defects in chloride channel CLC-5, is characterised by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal stones. Mechanisms leading to nephrocalcinosis are unknown. Using a murine collecting duct cell line (mIMCD-3), we confirm endogenous expression of mCLC-5. During transfection of antisense CLC-5, we ... More
Fluorescent high-content imaging allows the discrimination and quantitation of E-LDL-induced lipid droplets and Ox-LDL-generated phospholipidosis in human macrophages.
AuthorsGrandl M, Schmitz G,
JournalCytometry A
PubMed ID20014301
'Macrophage foam cells formed during uptake of atherogenic lipoproteins are a hallmark of atherosclerotic lesion development. In this study, human macrophages were incubated with two prototypic atherogenic LDL modifications enzymatically degraded LDL (E-LDL) and oxidized LDL (Ox-LDL) prepared from the same donor LDL. To detect differences in macrophage lipid storage, ... More
Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses.
AuthorsWiedemann A, Depoil D, Faroudi M, Valitutti S
JournalProc Natl Acad Sci U S A
PubMed ID16832064
'A longstanding paradox in the activation of cytotoxic T lymphocytes (CTL) arises from the observation that CTL recognize and rapidly destroy target cells with exquisite sensitivity despite the fact that cytokine production requires sustained signaling at the immunological synapse. Here we solve this paradox by showing that CTL establish sustained ... More
Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero.
AuthorsFrattini A, Blair HC, Sacco MG, Cerisoli F, Faggioli F, Catò EM, Pangrazio A, Musio A, Rucci F, Sobacchi C, Sharrow AC, Kalla SE, Bruzzone MG, Colombo R, Magli MC, Vezzoni P, Villa A
JournalProc Natl Acad Sci U S A
PubMed ID16195375
'Autosomal recessive osteopetrosis (ARO) is a paradigm for genetic diseases that cause severe, often irreversible, defects before birth. In ARO, osteoclasts cannot remove mineralized cartilage, bone marrow is severely reduced, and bone cannot be remodeled for growth. More than 50% of the patients show defects in the osteoclastic vacuolar-proton-pump subunit, ... More
Plasma membrane domains participate in pH banding of Chara internodal cells.
AuthorsSchmölzer PM, Höftberger M, Foissner I,
JournalPlant Cell Physiol
PubMed ID21659328
'We investigated the identity and distribution of cortical domains, stained by the endocytic marker FM 1-43, in branchlet internodal cells of the characean green algae Chara corallina and Chara braunii. Co-labeling with NBD C(6)-sphingomyelin, a plasma membrane dye, which is not internalized, confirmed their location in the plasma membrane, and ... More
Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling.
AuthorsFonseca BD, Diering GH, Bidinosti MA, Dalal K, Alain T, Balgi AD, Forestieri R, Nodwell M, Rajadurai CV, Gunaratnam C, Tee AR, Duong F, Andersen RJ, Orlowski J, Numata M, Sonenberg N, Roberge M,
JournalJ Biol Chem
PubMed ID22474287
'Mammalian target of rapamycin complex 1 (mTORC1) signaling is frequently dysregulated in cancer. Inhibition of mTORC1 is thus regarded as a promising strategy in the treatment of tumors with elevated mTORC1 activity. We have recently identified niclosamide (a Food and Drug Administration-approved antihelminthic drug) as an inhibitor of mTORC1 signaling. ... More
NAADP mobilizes calcium from the endoplasmic reticular Ca(2+) store in T-lymphocytes.
AuthorsSteen M, Kirchberger T, Guse AH
JournalJ Biol Chem
PubMed ID17446167
'The target calcium store of nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent endogenous calcium-mobilizing compound known to date, has been proposed to reside in the lysosomal compartment or in the endo/sarcoplasmic reticulum. This study was performed to test the hypothesis of a lysosomal versus an endoplasmic reticular calcium ... More
Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn.
AuthorsOber RJ, Martinez C, Vaccaro C, Zhou J, Ward ES
JournalJ Immunol
PubMed ID14764666
'The MHC class I-related receptor, FcRn, plays a central role in regulating the serum levels of IgG. FcRn is expressed in endothelial cells, suggesting that these cells may be involved in maintaining IgG levels. We have used live cell imaging of FcRn-green fluorescent protein transfected human endothelial cells to analyze ... More
Essential requirement for sphingosine kinase 2 in a sphingolipid apoptosis pathway activated by FTY720 analogues.
AuthorsDon AS, Martinez-Lamenca C, Webb WR, Proia RL, Roberts E, Rosen H
JournalJ Biol Chem
PubMed ID17400555
'The clinical immunosuppressant FTY720 is a sphingosine analogue that, once phosphorylated by sphingosine kinase 2 (Sphk2), is an agonist of multiple receptor subtypes for sphingosine 1-phosphate. Short exposures to FTY720 afford long term protection in lymphoproliferative and autoimmune disease models, presumably by inducing apoptosis in subsets of cells essential for ... More
A photoconvertible fluorescent reporter to track chaperone-mediated autophagy.
AuthorsKoga H, Martinez-Vicente M, Macian F, Verkhusha VV, Cuervo AM,
JournalNat Commun
PubMed ID21750540
'Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble proteins in lysosomes. CMA contributes to cellular quality control and is activated as part of the cellular response to different stressors. Defective CMA has been identified in ageing and different age-related diseases. Until now, CMA activity could only ... More
An insight into the mechanisms of the phototoxic response induced by cyamemazine in cultured fibroblasts and keratinocytes.
AuthorsMorlière P, Haigle J, Aissani K, Filipe P, Silva JN, Santus R
JournalPhotochem Photobiol
PubMed ID15068029
'The phototoxicity of cyamemazine (CMZ, Tercian), a neuroleptic of the phenothiazine family, has recently been reported in humans. CMZ has an absorbance maximum at 267 nm (molar absorptivity, 25,800 M(-1) cm(-1)) but a weaker molar absorptivity in the ultraviolet A (UV-A) region. CMZ exhibits a fluorescence with maximum emission at ... More
Lysosomal membrane permeabilization is an early event in Sigma-2 receptor ligand mediated cell death in pancreatic cancer.
'Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden ... More
Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR.
AuthorsLalli G, Schiavo G
JournalJ Cell Biol
PubMed ID11807088
'Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor ... More
Hepatitis C virus upregulates Beclin1 for induction of autophagy and activates mTOR signaling.
AuthorsShrivastava S, Bhanja Chowdhury J, Steele R, Ray R, Ray RB,
JournalJ Virol
PubMed ID22674982
'Hepatitis C virus (HCV) induces autophagosome formation in infected human hepatocytes. We have previously reported that HCV exploits autophagic machinery in favor of virus growth and survival in host cells (S. Shrivastava et al., Hepatology 53:406-414, 2011); however, the mechanisms for autophagy induction is poorly understood. In the present study, ... More
H-type dimer formation of fluorophores: a mechanism for activatable, in vivo optical molecular imaging.
AuthorsOgawa M, Kosaka N, Choyke PL, Kobayashi H,
JournalACS Chem Biol
PubMed ID19480464
'In vivo molecular imaging with target-specific activatable '
Taxol inhibits endosomal-lysosomal membrane trafficking at two distinct steps in CV-1 cells.
AuthorsSonee M, Barrón E, Yarber FA, Hamm-Alvarez SF
JournalAm J Physiol
PubMed ID9843725
'Although taxol inhibits membrane trafficking, the nature of this inhibition has not been well defined. In this study, we define the effects of taxol on endocytosis in CV-1 cells using density gradient centrifugation of membranes over sorbitol density gradients. After taxol treatment, resident endosomal enzymes and the epidermal growth factor ... More
Kinectin-kinesin binding domains and their effects on organelle motility.
AuthorsOng LL, Lim AP, Er CP, Kuznetsov SA, Yu H
JournalJ Biol Chem
PubMed ID10913441
'Intracellular organelle motility involves motor proteins that move along microtubules or actin filaments. One of these motor proteins, kinesin, was proposed to bind to kinectin on membrane organelles during movement. Whether kinectin is the kinesin receptor on organelles with a role in organelle motility has been controversial. We have characterized ... More
'The autophagic/lysosomal system includes a variety of vesicular compartments that undergo dynamic fusion events. However, the characteristics and factors modulating these interactions remain, for the most part, unknown. To gain insights on the properties that govern lysosomal fusion events, we have established an in vitro fusion assay using different lysosomal/autophagic ... More
Apoptosis and morphology in mouse embryos by confocal laser scanning microscopy.
AuthorsZucker RM, Hunter ES, Rogers JM
JournalMethods
PubMed ID10491277
'Confocal laser scanning microscopy combined with a vital stain was used to study apoptosis in organogenesis-stage mouse embryos. Apoptosis has previously been visualized in whole embryos using the vital dyes acridine orange, Nile blue sulfate, and neutral red. In the present study, mouse embryos were harvested on Gestation Day 9 ... More
Intracellular localization of the radiation enhancer motexafin gadolinium using interferometric Fourier fluorescence microscopy.
AuthorsWoodburn KW
JournalJ Pharmacol Exp Ther
PubMed ID11356908
'Motexafin gadolinium (MGd) is a unique therapeutic agent that localizes in cancer cells and increases tumor response to ionizing radiation and certain chemotherapeutics. The in vitro intracellular localization, accumulation, and retention of MGd in murine EMT6 mammary sarcoma and Rif-1 fibrosarcoma cell lines were studied using interferometric Fourier fluorescence microscopy. ... More
Association of stomatin with lipid bodies.
AuthorsUmlauf E, Csaszar E, Moertelmaier M, Schuetz GJ, Parton RG, Prohaska R
JournalJ Biol Chem
PubMed ID15024010
'The oligomeric lipid raft-associated integral protein stomatin normally localizes to the plasma membrane and the late endosomal compartment. Similar to the caveolins, it is targeted to lipid bodies (LBs) on overexpression. Endogenous stomatin also associates with LBs to a small extent. Green fluorescent protein-tagged stomatin (StomGFP) and the dominant-negative caveolin-3 ... More
Enhancement of autophagy during lytic replication by the Kaposi's sarcoma-associated herpesvirus replication and transcription activator.
AuthorsWen HJ, Yang Z, Zhou Y, Wood C,
JournalJ Virol
PubMed ID20484505
'Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host ... More
Quantitation of the lysosomotropic character of cationic amphiphilic drugs using the fluorescent basic amine Red DND-99.
AuthorsLemieux B, Percival MD, Falgueyret JP
JournalAnal Biochem
PubMed ID15051542
'Cationic amphiphilic drugs (CAD) containing a basic moiety often accumulate in lysosomes or other acidic subcellular compartments. This lysosomotropism is due to the protonation of the CAD within acidic organelles leading to the formation of a membrane-impermeable form. Highly lipophilic CADs show a greater propensity to accumulate than those with ... More
A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture.
AuthorsSparrow JR, Parish CA, Hashimoto M, Nakanishi K
JournalInvest Ophthalmol Vis Sci
PubMed ID10549662
'PURPOSE: To study A2E, a component of retinal pigmented epithelial (RPE) cell lipofuscin, after its internalization by cultured human RPE cells. METHODS: A2E was synthesized and incubated with an adult RPE cell line devoid of native lipofuscin. To investigate the cellular compartmentalization of A2E, cells were incubated simultaneously with A2E ... More
Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy.
'We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts. Here, we show that uPARAP/Endo180 has a key role in the degradation of collagen during mammary carcinoma progression. In the normal murine mammary gland, uPARAP/Endo180 is widely expressed in periductal fibroblast-like mesenchymal ... More
Effects of cytokines on mycobacterial phagosome maturation.
AuthorsVia LE, Fratti RA, McFalone M, Pagan-Ramos E, Deretic D, Deretic V
JournalJ Cell Sci
PubMed ID9490634
'One of the major mechanisms permitting intracellular pathogens to parasitize macrophages is their ability to alter maturation of the phagosome or affect its physical integrity. These processes are opposed by the host innate and adaptive immune defenses, and in many instances mononuclear phagocytes can be stimulated with appropriate cytokines to ... More
Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles.
AuthorsEkkapongpisit M, Giovia A, Nicotra G, Ozzano M, Caputo G, Isidoro C,
JournalInt J Nanomedicine
PubMed ID22605932
'For a safe ''in vivo'' biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases) play a pivotal role in the immune ... More
Nuclear localization of pyrrole-imidazole polyamide-fluorescein conjugates in cell culture.
AuthorsBest TP, Edelson BS, Nickols NG, Dervan PB
JournalProc Natl Acad Sci U S A
PubMed ID14519850
'A series of hairpin pyrrole-imidazole polyamide-fluorescein conjugates were synthesized and assayed for cellular localization. Thirteen cell lines, representing 11 human cancers, one human transformed kidney cell line, and one murine leukemia cell line, were treated with 5 microM polyamide-fluorescein conjugates for 10-14 h, then imaged by confocal laser scanning microscopy. ... More
Evidence for a non-replicative intracellular stage of nontypable Haemophilus influenzae in epithelial cells.
'Nontypable Haemophilus influenzae (NTHi) is a Gram-negative, non-capsulated human bacterial pathogen, a major cause of a repertoire of respiratory infections, and intimately associated with persistent lung bacterial colonization in patients suffering from chronic obstructive pulmonary disease (COPD). Despite its medical relevance, relatively little is known about its mechanisms of pathogenicity. ... More
Neuronal stimulation induces autophagy in hippocampal neurons that is involved in AMPA receptor degradation after chemical long-term depression.
AuthorsShehata M, Matsumura H, Okubo-Suzuki R, Ohkawa N, Inokuchi K,
JournalJ Neurosci
PubMed ID22836274
'Many studies have reported the roles played by regulated proteolysis in synaptic plasticity and memory, but the role of autophagy in neurons remains unclear. In mammalian cells, autophagy functions in the clearance of long-lived proteins and organelles and in adaptation to starvation. In neurons, although autophagy-related proteins (ATGs) are highly ... More
Lysosomal Sequestration (Trapping) of Lipophilic Amine (Cationic Amphiphilic) Drugs in Immortalized Human Hepatocytes (Fa2N-4 Cells).
AuthorsKazmi F, Hensley T, Pope C, Funk RS, Loewen GJ, Buckley DB, Parkinson A,
JournalDrug Metab Dispos
PubMed ID23378628
'Lipophilic (logP > 1) and amphiphilic drugs (also known as cationic amphiphilic drugs) with ionizable amines (pKa > 6) can accumulate in lysosomes, a process known as lysosomal trapping. This process contributes to presystemic extraction by lysosome-rich organs (such as liver and lung), which, together with the binding of lipophilic ... More
ISG15 deregulates autophagy in genotoxin-treated ataxia telangiectasia cells.
AuthorsDesai SD, Reed RE, Babu S, Lorio EA,
JournalJ Biol Chem
PubMed ID23212917
'Ataxia-telangiectasia (A-T) is a cerebellar neurodegenerative disorder; however, the basis for the neurodegeneration in A-T is not well established. Lesions in the ubiquitin and autophagy pathways are speculated to contribute to the neurodegeneration in other neurological diseases and may have a role in A-T neurodegeneration. Our recent studies revealed that ... More
Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface.
AuthorsWubbolts R, Fernandez-Borja M, Oomen L, Verwoerd D, Janssen H, Calafat J, Tulp A, Dusseljee S, Neefjes J
JournalJ Cell Biol
PubMed ID8909537
'Newly synthesized MHC class II molecules are sorted to lysosomal structures where peptide loading can occur. Beyond this point in biosynthesis, no MHC class II molecules have been detected at locations other than the cell surface. We studied this step in intracellular transport by visualizing MHC class II molecules in ... More
Dynamic patterns of apoptosis in the developing chicken heart.
AuthorsSchaefer KS, Doughman YQ, Fisher SA, Watanabe M
JournalDev Dyn
PubMed ID14991705
'The outflow tract (OFT) is abnormal in many congenital heart defects. One critical mechanism for morphogenesis of this complex structure is apoptosis. Chicken embryos (stages 19-38; ED4-10) stained with a fluorescent supravital lysosomal dye (LysoTracker Red; LTR) revealed the three-dimensional relationship between structural changes and apoptosis. The LTR staining peaked ... More
Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria.
AuthorsAnes E, Kühnel MP, Bos E, Moniz-Pereira J, Habermann A, Griffiths G
JournalNat Cell Biol
PubMed ID12942085
'Pathogenic mycobacteria such as Mycobacterium tuberculosis and Mycobacterium avium facilitate disease by surviving intracellularly within a potentially hostile environment: the macrophage phagosome. They inhibit phagosome maturation processes, including fusion with lysosomes, acidification and, as shown here, membrane actin assembly. An in vitro assay developed for latex bead phagosomes (LBPs) provided ... More
Human IRGM induces autophagy to eliminate intracellular mycobacteria.
AuthorsSingh SB, Davis AS, Taylor GA, Deretic V
JournalScience
PubMed ID16888103
Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense against intracellular pathogens. We found that the murine Irgm1 (LRG-47) guanosine triphosphatase induced autophagy and generated large autolysosomal organelles as a mechanism for the elimination of intracellular Mycobacterium tuberculosis. We also identified a function for a human IRG protein in ... More
Novel guanidine-containing molecular transporters based on lactose scaffolds: lipophilicity effect on the intracellular organellar selectivity.
AuthorsBiswas G, Jeon OY, Lee WS, Kim DC, Kim KT, Lee S, Chang S, Chung SK,
JournalChemistry
PubMed ID18770513
We have synthesized two lactose-based molecular transporters, each containing seven guanidine residues attached to the lactose scaffold through omega-aminocarboxylate linker chains of two different lengths, and have examined their cellular uptakes and intracellular and organellar localizations in HeLa cells, as well as their tissue distributions in mice. Both molecular transporters ... More
Decreased uptake of bodipy-labelled compounds in the presence of the nuclear stain, DRAQ5.
AuthorsSnyder DS, Garon CF
JournalJ Microsc
PubMed ID12950469
We have found the nuclear stain DRAQ5 to decrease the cellular uptake of a series of boron dipyrromethane (bodipy)-labelled compounds. This phenomenon is consistent between Lysotracker Green DND 26, Lysotracker Red DND 99 and bodipy-labelled mycolactone. Although DRAQ5 uptake was not prevented, DRAQ5 was in significant excess in each case. ... More
Nanotubular highways for intercellular organelle transport.
AuthorsRustom A, Saffrich R, Markovic I, Walther P, Gerdes HH
JournalScience
PubMed ID14963329
Cell-to-cell communication is a crucial prerequisite for the development and maintenance of multicellular organisms. To date, diverse mechanisms of intercellular exchange of information have been documented, including chemical synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive nanotubular structures formed de novo between cells that create complex networks. These ... More
Regulation of phagosome maturation by signals from toll-like receptors.
AuthorsBlander JM, Medzhitov R
JournalScience
PubMed ID15143282
In higher metazoans, phagocytosis is essential in host defense against microbial pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells are delivered on a common route from phagosomes to lysosomes for degradation. Here, we found that activation of the Toll-like receptor (TLR) signaling pathway by bacteria, but ... More
The von Hippel-Lindau tumor suppressor targets to mitochondria.
AuthorsShiao YH, Resau JH, Nagashima K, Anderson LM, Ramakrishna G
JournalCancer Res
PubMed ID10850420
Subcellular localization of von Hippel-Lindau (VHL) tumor suppressor may clarify its role in tumorigenesis. In rat kidney, we observed a granular cytoplasmic immunostaining of VHL, as seen in human tissues. The green fluorescent protein (GFP)-tagged VHL also appeared as cytoplasmic granules in vitro and was colocalized with a mitochondrion-selective dye. ... More
Rapid up-regulation and granule-independent transport of perforin to the immunological synapse define a novel mechanism of antigen-specific CD8+ T cell cytotoxic activity.
CTL are endowed with the ability to eliminate pathogens through perforin-mediated cytotoxic activity. The mechanism for perforin-mediated Ag-specific killing has been solely attributed to cytotoxic granule exocytosis from activated CD8(+) T cells. In this study, we redefine this mechanism, demonstrating that virus-specific CD8(+) T cells rapidly up-regulate perforin in response ... More
Controlling the intracellular localization of fluorescent polyamide analogues in cultured cells.
AuthorsCrowley KS, Phillion DP, Woodard SS, Schweitzer BA, Singh M, Shabany H, Burnette B, Hippenmeyer P, Heitmeier M, Bashkin JK
JournalBioorg Med Chem Lett
PubMed ID12699756
The intracellular distribution of fluorescent-labeled polyamides was examined in live cells. We showed that BODIPY-labeled polyamides accumulate in acidic vesicles, mainly lysosomes, in the cytoplasm of HCT116 colon cancer cells and human rheumatoid synovial fibroblasts (RSF). Verapamil blocked vesicular accumulation and led to nuclear accumulation of the BODIPY-labeled polyamide in ... More
Fluorescent histochemical techniques for analysis of intracellular signaling.
AuthorsOksvold MP, Skarpen E, Widerberg J, Huitfeldt HS
JournalJ Histochem Cytochem
PubMed ID11850432
Intracellular signaling relies on the orchestrated cooperation of signaling proteins and modules, their intracellular localization, and membrane trafficking. Recently, a repertoire of fluorescence-based techniques, which significantly increases our potential for detailed studies of the involved mechanisms, has been introduced. Microscopic techniques with increased resolution have been combined with improved techniques ... More
NAADP mobilizes Ca(2+) from reserve granules, lysosome-related organelles, in sea urchin eggs.
AuthorsChurchill GC, Okada Y, Thomas JM, Genazzani AA, Patel S, Galione A
JournalCell
PubMed ID12464181
Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca(2+) in many cells and species. Unlike other Ca(2+)-mobilizing messengers, NAADP mobilizes Ca(2+) from an unknown store that is not the endoplasmic reticulum, the store traditionally associated with messenger-mediated Ca(2+) signaling. Here, we demonstrate the presence of a Ca(2+) store in sea urchin ... More
Distinct roles of TIR and non-TIR regions in the subcellular localization and signaling properties of MyD88.
AuthorsNishiya T, Kajita E, Horinouchi T, Nishimoto A, Miwa S,
JournalFEBS Lett
PubMed ID17583698
MyD88 is a cytoplasmic adaptor protein that is critical for Toll-like receptor (TLR) signaling. The subcellular localization of MyD88 is characterized as large condensed forms in the cytoplasm. The mechanism and significance of this localization with respect to the signaling function, however, are currently unknown. Here, we demonstrate that MyD88 ... More
Monitoring autophagy in lysosomal storage disorders.
AuthorsRaben N, Shea L, Hill V, Plotz P,
JournalMethods Enzymol
PubMed ID19216919
Lysosomes are the final destination of the autophagic pathway. It is in the acidic milieu of the lysosomes that autophagic cargo is metabolized and recycled. One would expect that diseases with primary lysosomal defects would be among the first systems in which autophagy would be studied. In reality, this is ... More
OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway.
AuthorsJeannin P, Renno T, Goetsch L, Miconnet I, Aubry JP, Delneste Y, Herbault N, Baussant T, Magistrelli G, Soulas C, Romero P, Cerottini JC, Bonnefoy JY
JournalNat Immunol
PubMed ID11101872
We analyzed the interaction between a bacterial cell wall protein and dendritic cells (DCs). Outer membrane protein A from Klebsiella pneumoniae (kpOmpA) specifically bound to professional antigen presenting cells and was endocytosed by immature DCs via a receptor-dependent mechanism. kpOmpA signaled through Toll-like receptor 2, induced DCs to produce interleukin ... More
Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia.
AuthorsCho JY, Guo C, Torello M, Lunstrum GP, Iwata T, Deng C, Horton WA
JournalProc Natl Acad Sci U S A
PubMed ID14699054
Mutations of fibroblast growth factor receptor 3 (FGFR3) are responsible for achondroplasia (ACH) and related dwarfing conditions in humans. The pathogenesis involves constitutive activation of FGFR3, which inhibits proliferation and differentiation of growth plate chondrocytes. Here we report that activating mutations in FGFR3 increase the stability of the receptor. Our ... More
Inhibitors of intravesicular acidification protect against Shiga toxin in a pH-independent manner.
AuthorsDyve Lingelem AB, Bergan J, Sandvig K,
JournalTraffic
PubMed ID22132807
Shiga toxin inhibits protein synthesis after being transported from the cell surface to endosomes and retrogradely through the Golgi apparatus to the endoplasmic reticulum (ER) and into the cytosol. In this study, we have abolished proton gradients across internal membranes in different ways and investigated the effect on the various ... More
The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases.
AuthorsUngewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW
JournalProc Natl Acad Sci U S A
PubMed ID16365287
Numerous inositol polyphosphate 5-phosphatases catalyze the degradation of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P(2)) to phosphatidylinositol-4-phosphate (PtdIns-4-P). An alternative pathway to degrade PtdIns-4,5-P(2) is the hydrolysis of PtdIns-4,5-P(2) by a 4-phosphatase, leading to the production of PtdIns-5-P. Whereas the bacterial IpgD enzyme is known to catalyze this reaction, no such mammalian enzyme has been ... More
Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases.
AuthorsWang Z, Zhang J, Wang Y, Xing R, Yi C, Zhu H, Chen X, Guo J, Guo W, Li W, Wu L, Lu Y, Liu S,
JournalCarcinogenesis
PubMed ID23002236
Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese ... More
PEG-nanolized ultrasmall selenium nanoparticles overcome drug resistance in hepatocellular carcinoma HepG2 cells through induction of mitochondria dysfunction.
AuthorsZheng S, Li X, Zhang Y, Xie Q, Wong YS, Zheng W, Chen T,
JournalInt J Nanomedicine
PubMed ID22915845
Gray selenium (Se) is one of the most widely used Se sources with very limited biocompatibility and bioactivity. In the present study, a simple method for the preparation of ultrasmall selenium nanoparticles (SeNPs) through direct nanolization of gray selenium by polyethylene glycol (PEG) was demonstrated. Monodisperse and homogeneous PEG-SeNPs with ... More
Drosophila Golgi membrane protein Ema promotes autophagosomal growth and function.
AuthorsKim S, Naylor SA, DiAntonio A,
JournalProc Natl Acad Sci U S A
PubMed ID22493244
Autophagy is a self-degradative process in which cellular material is enclosed within autophagosomes and trafficked to lysosomes for degradation. Autophagosomal biogenesis is well described; however mechanisms controlling the growth and ultimate size of autophagosomes are unclear. Here we demonstrate that the Drosophila membrane protein Ema is required for the growth ... More
Global analysis of the transcriptional response of whitefly to tomato yellow leaf curl China virus reveals the relationship of coevolved adaptations.
AuthorsLuan JB, Li JM, Varela N, Wang YL, Li FF, Bao YY, Zhang CX, Liu SS, Wang XW,
JournalJ Virol
PubMed ID21270146
The begomoviruses are the largest and most economically important group of plant viruses transmitted exclusively by the whitefly Bemisia tabaci in a circulative, persistent manner. The circulation of the viruses within the insect vectors involves complex interactions between virus and vector components; however, the molecular mechanisms of these interactions remain ... More
Heavy ion irradiation induces autophagy in irradiated C2C12 myoblasts and their bystander cells.
AuthorsHino M, Hamada N, Tajika Y, Funayama T, Morimura Y, Sakashita T, Yokota Y, Fukamoto K, Mutou Y, Kobayashi Y, Yorifuji H,
JournalJ Electron Microsc (Tokyo)
PubMed ID20685830
Autophagy is one of the major processes involved in the degradation of intracellular materials. Here, we examined the potential impact of heavy ion irradiation on the induction of autophagy in irradiated C2C12 mouse myoblasts and their non-targeted bystander cells. In irradiated cells, ultrastructural analysis revealed the accumulation of autophagic structures ... More
The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma.
Antiapoptotic Bcl-2 family members suppress both apoptosis and autophagy and are of major importance for therapy resistance of malignant gliomas. To target these molecules, we used BH3 mimetics and analyzed the molecular mechanisms of cell death induced thereby. Glioma cells displayed only limited sensitivity to single-agent treatment with the BH3 ... More