Inhibition of caveolar uptake, SV40 infection, and beta1-integrin signaling by a nonnatural glycosphingolipid stereoisomer.
AuthorsSingh RD, Holicky EL, Cheng ZJ, Kim SY, Wheatley CL, Marks DL, Bittman R, Pagano RE
JournalJ Cell Biol
PubMed ID17371832
'Caveolar endocytosis is an important mechanism for the uptake of certain pathogens and toxins and also plays a role in the internalization of some plasma membrane (PM) lipids and proteins. However, the regulation of caveolar endocytosis is not well understood. We previously demonstrated that caveolar endocytosis and beta1-integrin signaling are ... More
The long and the short cycle. Alternative intracellular routes for trafficking of G-protein-coupled receptors.
AuthorsInnamorati G, Le Gouill C, Balamotis M, Birnbaumer M
JournalJ Biol Chem
PubMed ID11150299
'The C terminus of the human V2 vasopressin receptor contains multiple phosphorylation sites including a cluster of amino acids that when phosphorylated prevents the return of the internalized receptor to the cell surface. To identify the step where the recycling process was interrupted, the trafficking of the V2 receptor was ... More
Transfer of M2 muscarinic acetylcholine receptors to clathrin-derived early endosomes following clathrin-independent endocytosis.
AuthorsDelaney KA, Murph MM, Brown LM, Radhakrishna H
JournalJ Biol Chem
PubMed ID12093817
'Upon agonist stimulation, many G protein-coupled receptors such as beta(2)-adrenergic receptors are internalized via beta-arrestin- and clathrin-dependent mechanisms, whereas others, like M(2) muscarinic acetylcholine receptors (mAChRs), are internalized by clathrin- and arrestin-independent mechanisms. To gain further insight into the mechanisms that regulate M(2) mAChR endocytosis, we investigated the post-endocytic trafficking ... More
Identification and characterization of small molecules that inhibit intracellular toxin transport.
AuthorsSaenz JB, Doggett TA, Haslam DB
JournalInfect Immun
PubMed ID17576758
'Shiga toxin (Stx), cholera toxin (Ctx), and the plant toxin ricin are among several toxins that reach their intracellular destinations via a complex route. Following endocytosis, these toxins travel in a retrograde direction through the endosomal system to the trans-Golgi network, Golgi apparatus, and endoplasmic reticulum (ER). There the toxins ... More
A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating.
AuthorsMassol RH, Boll W, Griffin AM, Kirchhausen T
JournalProc Natl Acad Sci U S A
PubMed ID16798879
'Clathrin-coated pits assemble on a membrane and pinch off as coated vesicles. The released vesicles then rapidly lose their clathrin coats in a process mediated by the ATPase Hsc70, recruited by auxilin, a J-domain-containing cofactor. How is the uncoating process regulated? We find that during coat assembly small and variable ... More
Endosomal localization of the serum resistance-associated protein in African trypanosomes confers human infectivity.
AuthorsStephens NA, Hajduk SL,
JournalEukaryot Cell
PubMed ID21705681
'Trypanosoma brucei rhodesiense is the causative agent of human African sleeping sickness. While the closely related subspecies T. brucei brucei is highly susceptible to lysis by a subclass of human high-density lipoproteins (HDL) called trypanosome lytic factor (TLF), T. brucei rhodesiense is resistant and therefore able to establish acute and ... 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
Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes.
AuthorsKrauss M, Kukhtina V, Pechstein A, Haucke V
JournalProc Natl Acad Sci U S A
PubMed ID16880396
'Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P(2)] is an important factor for a variety of cellular functions ranging from cell signaling to actin cytoskeletal dynamics and endocytic membrane traffic. Here, we have identified the clathrin adaptor complex AP-2 as a regulator of phosphatidylinositol 4-phosphate 5-kinase (PIPK)-mediated PI(4,5)P(2) synthesis. AP-2 directly interacts with the kinase ... More
Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15.
Hrs-2, via interactions with SNAP-25, plays a regulatory role on the exocytic machinery. We now show that Hrs-2 physically interacts with Eps15, a protein required for receptor-mediated endocytosis. The Hrs-2/Eps15 interaction is calcium dependent, inhibited by SNAP-25 and alpha-adaptin, and results in the inhibition of receptor-mediated endocytosis. Immunoelectron microscopy reveals ... 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
Multivalent cyclic RGD conjugates for targeted delivery of small interfering RNA.
AuthorsAlam MR, Ming X, Fisher M, Lackey JG, Rajeev KG, Manoharan M, Juliano RL,
JournalBioconjug Chem
PubMed ID21755983
We have designed, synthesized, and tested conjugates of chemically modified luciferase siRNA (Luc-siRNA) with bi-, tri-, and tetravalent cyclic(arginine-glycine-aspartic) (cRGD) peptides that selectively bind to the avß3 integrin. The cellular uptake, subcellular distribution, and pharmacological effects of the cRGD-conjugated Luc-siRNAs compared to those of unconjugated controls were examined using a ... More
AT1 receptor-mediated accumulation of extracellular angiotensin II in proximal tubule cells: role of cytoskeleton microtubules and tyrosine phosphatases.
AuthorsLi XC, Carretero OA, Navar LG, Zhuo JL,
JournalAm J Physiol Renal Physiol
PubMed ID16478976
Long-term angiotensin II (ANG II) administration is associated with increased ANG II accumulation in the kidney, but intrarenal compartment(s) involved in this response remains to be determined. We tested the hypothesis that 1) extracellular ANG II is taken up by proximal tubule cells (PTCs) through AT(1) receptor-mediated endocytosis, 2) this ... More
Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi.
AuthorsBrown LR, Harris DA
JournalJ Neurochem
PubMed ID14511113
The cellular isoform of prion protein (PrPC) is a plasma membrane glycoprotein whose conformational conversion into PrPSc is the central molecular event in the propagation of infectious prions. However, the physiological function of PrPC has remained uncertain. The finding that PrPC binds copper ions with low micromolar affinity, coupled with ... More
TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2.
AuthorsHayes S, Chawla A, Corvera S
JournalJ Cell Biol
PubMed ID12356868
Transforming growth factor (TGF)beta is an important physiological regulator of cellular growth and differentiation. It activates a receptor threonine/serine kinase that phosphorylates the transcription factor Smad2, which then translocates into the nucleus to trigger specific transcriptional events. Here we show that activated type I and II TGF beta receptors internalize ... More
Early endosomal localization of hrs requires a sequence within the proline- and glutamine-rich region but not the FYVE finger.
AuthorsHayakawa A, Kitamura N
JournalJ Biol Chem
PubMed ID10889197
Hrs is an early endosomal protein that is tyrosine-phosphorylated in cells stimulated with growth factors. Hrs is thought to play a regulatory role in endocytosis of growth factor-receptor complexes through early endosomes. Early endosomal localization of Hrs seems to be essential for Hrs to exert its function in the endocytosis. ... More
Endosomal recycling controls plasma membrane area during mitosis.
AuthorsBoucrot E, Kirchhausen T
JournalProc Natl Acad Sci U S A
PubMed ID17483462
The shape and total surface of a cell and its daughters change during mitosis. Many cells round up during prophase and metaphase and reacquire their extended and flattened shape during cytokinesis. How does the total area of plasma membrane change to accommodate these morphological changes and by what mechanism is ... More
Endocytosed transferrin receptors recycle via distinct dynamin and phosphatidylinositol 3-kinase-dependent pathways.
Authorsvan Dam EM, Ten Broeke T, Jansen K, Spijkers P, Stoorvogel W
JournalJ Biol Chem
PubMed ID12372835
Recycling of endocytosed membrane proteins involves passage through early endosomes and recycling endosomes. Previously, we demonstrated a role for clathrin-coated vesicles in transferrin receptor recycling. These clathrin-coated vesicles are formed from recycling endosomes in a process that was inhibited in dynamin-1(G273D)-overexpressing cells. Here we show a second transferrin recycling pathway, ... More
Cardiac steroids induce changes in recycling of the plasma membrane in human NT2 cells.
AuthorsRosen H, Glukhman V, Feldmann T, Fridman E, Lichtstein D
JournalMol Biol Cell
PubMed ID14718569
Cardiac steroids (CSs) are specific inhibitors of Na+, K(+)-ATPase activity. Although the presence of CS-like compounds in animal tissues has been established, their physiological role is not evident. In the present study, treatment of human NT2 cells with physiological concentrations (nanomolar) of CSs caused the accumulation of large vesicles adjacent ... More
The Rab5 activator ALS2/alsin acts as a novel Rac1 effector through Rac1-activated endocytosis.
AuthorsKunita R, Otomo A, Mizumura H, Suzuki-Utsunomiya K, Hadano S, Ikeda JE
JournalJ Biol Chem
PubMed ID17409386
Mutations in the ALS2 gene cause a number of recessive motor neuron diseases, indicating that the ALS2 protein (ALS2/alsin) is vital for motor neurons. ALS2 acts as a guanine nucleotide exchange factor (GEF) for Rab5 (Rab5GEF) and is involved in endosome dynamics. However, the spatiotemporal regulation of the ALS2-mediated Rab5 ... More
Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI.
AuthorsNieland TJ, Penman M, Dori L, Krieger M, Kirchhausen T
JournalProc Natl Acad Sci U S A
PubMed ID12438696
The high-density lipoprotein (HDL) receptor, scavenger receptor, class B, type I (SR-BI), mediates both the selective uptake of lipids, mainly cholesterol esters, from HDL to cells and the efflux of cholesterol from cells to lipoproteins. The mechanism underlying these lipid transfers is distinct from classic receptor-mediated endocytosis, but it remains ... More
Transferrin receptor recycling in the absence of perinuclear recycling endosomes.
AuthorsSheff D, Pelletier L, O'Connell CB, Warren G, Mellman I
JournalJ Cell Biol
PubMed ID11877458
In mammalian cells, internalized receptors such as transferrin (Tfn) receptor are presumed to pass sequentially through early endosomes (EEs) and perinuclear recycling endosomes (REs) before returning to the plasma membrane. Whether passage through RE is obligatory, however, remains unclear. Kinetic analysis of endocytosis in CHO cells suggested that the majority ... More
The role of LIP5 and CHMP5 in multivesicular body formation and HIV-1 budding in mammalian cells.
AuthorsWard DM, Vaughn MB, Shiflett SL, White PL, Pollock AL, Hill J, Schnegelberger R, Sundquist WI, Kaplan J
JournalJ Biol Chem
PubMed ID15644320
We examined the function of LIP5 in mammalian cells, because the yeast homologue Vta1p was recently identified as a protein required for multivesicular body (MVB) formation. LIP5 is predominantly a cytosolic protein. Depletion of LIP5 by small inhibitory RNA (siRNA) does not affect the distribution or morphology of early endosomes, ... More
Increased internalization of p120-uncoupled E-cadherin and a requirement for a dileucine motif in the cytoplasmic domain for endocytosis of the protein.
AuthorsMiyashita Y, Ozawa M
JournalJ Biol Chem
PubMed ID17298950
E-cadherin is a member of the cadherin family of Ca2+-dependent cell-cell adhesion molecules. E-cadherin associates with beta-catenin at the membrane-distal region of its cytosolic domain and with p120 at the membrane-proximal region of its cytoplasmic domain. It has been shown that a pool of cell surface E-cadherin is constitutively internalized ... More
Antigen-stimulated trafficking from the recycling compartment to the plasma membrane in RBL mast cells.
AuthorsNaal RM, Holowka EP, Baird B, Holowka D
JournalTraffic
PubMed ID12656991
Binding of fluorescein isothiocyanate (FITC)-conjugated cholera toxin B subunit to ganglioside GM1 on RBL-2H3 cells at 37 degrees C results in labeling of the plasma membrane as well as a pool of perinuclear intracellular membranes identified as the endosomal recycling compartment. Antigen-mediated activation of IgE receptor signaling causes rapid, sustained ... More
Role of the Phox homology domain and phosphorylation in activation of serum and glucocorticoid-regulated kinase-3.
AuthorsTessier M, Woodgett JR
JournalJ Biol Chem
PubMed ID16790420
Serum and glucocorticoid-regulated kinases (SGKs) form a family of serine/threonine protein kinases that exhibit structural and sequence similarity to the protein kinase B (PKB)/Akt family. The major difference between these two families is the absence of a lipid-binding, pleckstrin homology domain in the SGKs. Despite the absence of the pleckstrin ... More
Differential PI 3-kinase dependence of early and late phases of recycling of the internalized AT1 angiotensin receptor.
AuthorsHunyady L, Baukal AJ, Gaborik Z, Olivares-Reyes JA, Bor M, Szaszak M, Lodge R, Catt KJ, Balla T
JournalJ Cell Biol
PubMed ID12070129
Agonist-induced endocytosis and processing of the G protein-coupled AT1 angiotensin II (Ang II) receptor (AT1R) was studied in HEK 293 cells expressing green fluorescent protein (GFP)- or hemagglutinin epitope-tagged forms of the receptor. After stimulation with Ang II, the receptor and its ligand colocalized with Rab5-GFP and Rab4-GFP in early ... More
Differential effects of modification of membrane cholesterol and sphingolipids on the conformation, function, and trafficking of the G protein-coupled cholecystokinin receptor.
AuthorsHarikumar KG, Puri V, Singh RD, Hanada K, Pagano RE, Miller LJ
JournalJ Biol Chem
PubMed ID15537636
The lipid microenvironment of receptors can influence their conformation, function, and regulation. Cholecystokinin (CCK)-stimulated signaling is abnormal in some forms of hyperlipidemia, suggesting the possibility of unique sensitivity to its lipid environment. Here we examined the influence of cholesterol and sphingolipids on CCK receptors in model Chinese hamster ovary cell ... More
P-glycoprotein does not reduce substrate concentration from the extracellular leaflet of the plasma membrane in living cells.
AuthorsChen Y, Pant AC, Simon SM
JournalCancer Res
PubMed ID11691790
P-glycoprotein (Pgp), a member of the ATP-binding cassette family of transporters, is an important mediator of multidrug resistance in cancer. Pgp exhibits a very broad specificity for substrates. These substrates share a common feature of being amphipathic and can orient into either leaflet of the membrane bilayer. Current evidence suggests ... More
The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells.
AuthorsPitts KR, Yoon Y, Krueger EW, McNiven MA
JournalMol Biol Cell
PubMed ID10588666
The dynamin family of large GTPases has been implicated in vesicle formation from both the plasma membrane and various intracellular membrane compartments. The dynamin-like protein DLP1, recently identified in mammalian tissues, has been shown to be more closely related to the yeast dynamin proteins Vps1p and Dnm1p (42%) than to ... More
Tyrphostin A23 inhibits internalization of the transferrin receptor by perturbing the interaction between tyrosine motifs and the medium chain subunit of the AP-2 adaptor complex.
AuthorsBanbury DN, Oakley JD, Sessions RB, Banting G
JournalJ Biol Chem
PubMed ID12556528
Several intracellular membrane trafficking events are mediated by tyrosine-containing motifs within the cytosolic domains of integral membrane proteins. Many such motifs conform to the consensus YXXPhi, where Phi represents a bulky hydrophobic residue. This motif interacts with the medium chain (mu) subunits of adaptor complexes that link the cytosolic domains ... More
H-Ras dynamically interacts with recycling endosomes in CHO-K1 cells: involvement of Rab5 and Rab11 in the trafficking of H-Ras to this pericentriolar endocytic compartment.
AuthorsGomez GA, Daniotti JL
JournalJ Biol Chem
PubMed ID16079139
H-, N-, and K-Ras are isoforms of Ras proteins, which undergo different lipid modifications at the C terminus. These post-translational events make possible the association of Ras proteins both with the inner plasma membrane and to the cytosolic surface of endoplasmic reticulum and Golgi complex, which is also required for ... More
Cell-type-dependent targeting of human immunodeficiency virus type 1 assembly to the plasma membrane and the multivesicular body.
AuthorsOno A, Freed EO
JournalJ Virol
PubMed ID14722309
The human immunodeficiency virus type 1 (HIV-1) assembly-and-release pathway begins with the targeting of the Gag precursor to the site of virus assembly. The molecular mechanism by which Gag is targeted to the appropriate subcellular location remains poorly understood. Based on the analysis of mutant Gag proteins, we and others ... More
Half-life-extended recombinant coagulation factor IX-albumin fusion protein is recycled via the FcRn-mediated pathway.
Authors
JournalJ Biol Chem
PubMed ID29523681
Rab22A recruits BLOC-1 and BLOC-2 to promote the biogenesis of recycling endosomes.
Authors
JournalEMBO Rep
PubMed ID30404817
The STX6-VTI1B-VAMP3 complex facilitates xenophagy by regulating the fusion between recycling endosomes and autophagosomes.
Authors
JournalAutophagy
PubMed ID27791468
SNAP23 regulates BAX-dependent adipocyte programmed cell death independently of canonical macroautophagy.
Authors
JournalJ Clin Invest
PubMed ID30102258
Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling.
Authors
JournalJ Virol
PubMed ID24599995
Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis.
Authors
JournalDevelopment
PubMed ID24598168
ATG16L1 autophagy pathway regulates BAX protein levels and programmed cell death.
Authors
JournalJ Biol Chem
PubMed ID32848017
Autophagy and formation of tubulovesicular autophagosomes provide a barrier against nonviral gene delivery.
Authors
JournalAutophagy
PubMed ID23422759
Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors.
Authors
JournalElife
PubMed ID34796874
Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids.