Neutrophils are highly motile leukocytes, and they play important roles in the innate immune response to invading pathogens. Neutrophil chemotaxis requires Rac activation, yet the Rac activators functioning downstream of chemoattractant receptors remain to be determined. We show that DOCK2, which is a mammalian homologue of Caenorhabditis elegans CED-5 and ... More
Dual channel STED nanoscopy of lytic granules on actin filaments in natural killer cells.
AuthorsMace EM, Orange JS,
JournalCommun Integr Biol
PubMed ID22808328
Natural killer (NK) cells are innate immune effectors that eliminate diseased and tumorigenic targets through the directed secretion of specialized secretory lysosomes, termed lytic granules. This directed secretion is triggered following the formation of an immunological synapse (IS), which is characterized by actin re-modeling and receptor organization at the interface ... More
Actin polymerization controls the activation of multidrug efflux at fertilization by translocation and fine-scale positioning of ABCB1 on microvilli.
AuthorsWhalen K, Reitzel AM, Hamdoun A,
JournalMol Biol Cell
PubMed ID22855533
Fertilization changes the structure and function of the cell surface. In sea urchins, these changes include polymerization of cortical actin and a coincident, switch-like increase in the activity of the multidrug efflux transporter ABCB1a. However, it is not clear how cortical reorganization leads to changes in membrane transport physiology. In ... More
PKC-induced intracellular trafficking of Ca(V)2 precedes its rapid recruitment to the plasma membrane.
AuthorsZhang Y, Helm JS, Senatore A, Spafford JD, Kaczmarek LK, Jonas EA,
JournalJ Neurosci
PubMed ID18322103
'Activation of protein kinase C (PKC) potentiates secretion in Aplysia peptidergic neurons, in part by inducing new sites for peptide release at growth cone terminals. The mechanisms by which ion channels are trafficked to such sites are, however, not well understood. We now show that PKC activation rapidly recruits new ... More
Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation.
AuthorsJoshi B, Bastiani M, Strugnell SS, Boscher C, Parton RG, Nabi IR,
JournalJ Cell Biol
PubMed ID23091071
'Caveolin-1 (Cav1) is an essential component of caveolae whose Src kinase-dependent phosphorylation on tyrosine 14 (Y14) is associated with regulation of focal adhesion dynamics. However, the relationship between these disparate functions remains to be elucidated. Caveola biogenesis requires expression of both Cav1 and cavin-1, but Cav1Y14 phosphorylation is dispensable. In ... More
The keratin-binding protein Albatross regulates polarization of epithelial cells.
AuthorsSugimoto M, Inoko A, Shiromizu T, Nakayama M, Zou P, Yonemura S, Hayashi Y, Izawa I, Sasoh M, Uji Y, Kaibuchi K, Kiyono T, Inagaki M,
JournalJ Cell Biol
PubMed ID18838552
'The keratin intermediate filament network is abundant in epithelial cells, but its function in the establishment and maintenance of cell polarity is unclear. Here, we show that Albatross complexes with Par3 to regulate formation of the apical junctional complex (AJC) and maintain lateral membrane identity. In nonpolarized epithelial cells, Albatross ... More
Augmentation in expression of activation-induced genes differentiates memory from naive CD4+ T cells and is a molecular mechanism for enhanced cellular response of memory CD4+ T cells.
AuthorsLiu K, Li Y, Prabhu V, Young L, Becker KG, Munson PJ, Weng Np
JournalJ Immunol
PubMed ID11390484
'In an attempt to understand the molecular basis for the immunological memory response, we have used cDNA microarrays to measure gene expression of human memory and naive CD4+ T cells at rest and after activation. Our analysis of 54,768 cDNA clones provides the first glimpse into gene expression patterns of ... More
Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.
AuthorsGiannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI,
JournalProc Natl Acad Sci U S A
PubMed ID18332421
'We have characterized the adaptations of Helicobacter pylori to a rarely captured event in the evolution of its impact on host biology-the transition from chronic atrophic gastritis (ChAG) to gastric adenocarcinoma-and defined the impact of these adaptations on an intriguing but poorly characterized interaction between this bacterium and gastric epithelial ... More
A putative Src homology 3 domain binding motif but not the C-terminal dystrophin WW domain binding motif is required for dystroglycan function in cellular polarity in Drosophila.
AuthorsYatsenko AS, Gray EE, Shcherbata HR, Patterson LB, Sood VD, Kucherenko MM, Baker D, Ruohola-Baker H
JournalJ Biol Chem
PubMed ID17355978
'The conserved dystroglycan-dystrophin (Dg.Dys) complex connects the extracellular matrix to the cytoskeleton. In humans as well as Drosophila, perturbation of this complex results in muscular dystrophies and brain malformations and in some cases cellular polarity defects. However, the regulation of the Dg.Dys complex is poorly understood in any cell type. ... More
Pygmy squids and giant brains: mapping the complex cephalopod CNS by phalloidin staining of vibratome sections and whole-mount preparations.
AuthorsWollesen T, Loesel R, Wanninger A,
JournalJ Neurosci Methods
PubMed ID19428513
'Among bilaterian invertebrates, cephalopod molluscs (e.g., squids, cuttlefish and octopuses) have a central nervous system (CNS) that rivals in complexity that of the phylogenetically distant vertebrates (e.g., mouse and human). However, this prime example of convergent evolution has rarely been the subject of recent developmental and evolutionary studies, which may ... More
CD28-stimulated ERK2 phosphorylation is required for polarization of the microtubule organizing center and granules in YTS NK cells.
AuthorsChen X, Allan DS, Krzewski K, Ge B, Kopcow H, Strominger JL
JournalProc Natl Acad Sci U S A
PubMed ID16801532
'Activation of natural killer (NK) cell cytotoxicity requires adhesion and formation of a conjugate with a susceptible target cell, followed by actin polymerization, and polarization of the microtubule organizing center (MTOC) and cytolytic granules to the NK cell immune synapse. Here, by using the YTS NK cell line as a ... More
Protein synthesis in distal axons is not required for growth cone responses to guidance cues.
AuthorsRoche FK, Marsick BM, Letourneau PC,
JournalJ Neurosci
PubMed ID19158291
'Recent evidence suggests that growth cone responses to guidance cues require local protein synthesis. Using chick neurons, we investigated whether protein synthesis is required for growth cones of several types to respond to guidance cues. First, we found that global inhibition of protein synthesis stops axonal elongation after 2 h. ... More
Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells.
AuthorsOsakada F, Ikeda H, Mandai M, Wataya T, Watanabe K, Yoshimura N, Akaike A, Akaike A, Sasai Y, Takahashi M,
JournalNat Biotechnol
PubMed ID18246062
'We previously reported the differentiation of mouse embryonic stem (ES) cells into retinal progenitors. However, these progenitors rarely differentiate into photoreceptors unless they are cultured with embryonic retinal tissues. Here we show the in vitro generation of putative rod and cone photoreceptors from mouse, monkey and human ES cells by ... More
Alexa dyes, a series of new fluorescent dyes that yield exceptionally bright, photostable conjugates.
AuthorsPanchuk-Voloshina N, Haugland RP, Bishop-Stewart J, Bhalgat MK, Millard PJ, Mao F, Leung WY, Haugland RP
JournalJ Histochem Cytochem
PubMed ID10449539
'Alexa 350, Alexa 430, Alexa 488, Alexa 532, Alexa 546, Alexa 568, and Alexa 594 dyes are a new series of fluorescent dyes with emission/excitation spectra similar to those of AMCA, Lucifer Yellow, fluorescein, rhodamine 6G, tetramethylrhodamine or Cy3, lissamine rhodamine B, and Texas Red, respectively (the numbers in the ... More
Persistent cAMP-signals triggered by internalized G-protein-coupled receptors.
'G-protein-coupled receptors (GPCRs) are generally thought to signal to second messengers like cyclic AMP (cAMP) from the cell surface and to become internalized upon repeated or prolonged stimulation. Once internalized, they are supposed to stop signaling to second messengers but may trigger nonclassical signals such as mitogen-activated protein kinase (MAPK) ... More
Invasive Escherichia coli are a feature of Crohn's disease.
AuthorsSasaki M, Sitaraman SV, Babbin BA, Gerner-Smidt P, Ribot EM, Garrett N, Alpern JA, Akyildiz A, Theiss AL, Nusrat A, Klapproth JM
JournalLab Invest
PubMed ID17660846
'Crohn's disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory conditions of the gut. Our goal was to investigate if invasive Escherichia coli strains were present in patients with inflammatory bowel disease (IBD). Bacterial strains were isolated from biopsy material obtained from normal controls, and patients with a clinical diagnosis ... More
CHO1, a mammalian kinesin-like protein, interacts with F-actin and is involved in the terminal phase of cytokinesis.
AuthorsKuriyama R, Gustus C, Terada Y, Uetake Y, Matuliene J
JournalJ Cell Biol
PubMed ID11877456
'CHO1 is a kinesin-like protein of the mitotic kinesin-like protein (MKLP)1 subfamily present in central spindles and midbodies in mammalian cells. It is different from other subfamily members in that it contains an extra approximately 300 bp in the COOH-terminal tail. Analysis of the chicken genomic sequence showed that heterogeneity ... More
Regulated expression of nullo is required for the formation of distinct apical and basal adherens junctions in the Drosophila blastoderm.
AuthorsHunter C, Wieschaus E
JournalJ Cell Biol
PubMed ID10908580
'During cellularization, the Drosophila embryo undergoes a large-scale cytokinetic event that packages thousands of syncytial nuclei into individual cells, resulting in the de novo formation of an epithelial monolayer in the cortex of the embryo. The formation of adherens junctions is one of the many aspects of epithelial polarity that ... More
Differential responses to nerve growth factor and epidermal growth factor in neurite outgrowth of PC12 cells are determined by Rac1 activation systems.
AuthorsYasui H, Katoh H, Yamaguchi Y, Aoki J, Fujita H, Mori K, Negishi M
JournalJ Biol Chem
PubMed ID11278419
'Neurite outgrowth of PC12 cells is induced by nerve growth factor (NGF) but not by epidermal growth factor (EGF). This differential response has been explained by the duration of mitogen-activated protein kinase (MAPK) activation; NGF induces sustained MAPK activation but EGF leads short-lived activation. However, precise mechanisms have not yet ... More
PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration.
AuthorsZeng L, Si X, Yu WP, Le HT, Ng KP, Teng RM, Ryan K, Wang DZ, Ponniah S, Pallen CJ
JournalJ Cell Biol
PubMed ID12515828
'We investigated the molecular and cellular actions of receptor protein tyrosine phosphatase (PTP) alpha in integrin signaling using immortalized fibroblasts derived from wild-type and PTP alpha-deficient mouse embryos. Defects in PTP alpha-/- migration in a wound healing assay were associated with altered cell shape and focal adhesion kinase (FAK) phosphorylation. ... More
Intravital two-photon microscopy for studying the uptake and trafficking of fluorescently conjugated molecules in live rodents.
AuthorsMasedunskas A, Weigert R,
JournalTraffic
PubMed ID18647170
'In this study, we describe an experimental system based on intravital two-photon microscopy for studying endocytosis in live animals. The rodent submandibular glands were chosen as model organs because they can be exposed easily, imaged without compromising their function and, furthermore, they are amenable to pharmacological and genetic manipulations. We ... More
Aggregation of f-actin in olfactory glomeruli: a common feature of glomeruli across phyla.
AuthorsRössler W, Kuduz J, Schürmann FW, Schild D
JournalChem Senses
PubMed ID12438205
'Using fluorophore-conjugated phalloidin, we show that filamentous (F)-actin is strongly aggregated in olfactory glomeruli within primary olfactory centers of vertebrates and insects. Our comparative study demonstrates that aggregation of F-actin is a common feature of glomeruli across phyla, and is independent of glomerular architecture and/or the presence or absence of ... More
LMP4 regulates Tbx5 protein subcellular localization and activity.
AuthorsCamarata T, Bimber B, Kulisz A, Chew TL, Yeung J, Simon HG
JournalJ Cell Biol
PubMed ID16880269
'The limb- and heart-specific Tbx5 transcription factor coexpresses with and directly binds to the novel PDZ-LIM domain protein, LMP4. LMP4 is distributed in the cytoplasm associated with the actin cytoskeleton. In the presence of LMP4, Tbx5 shuttles dynamically between the nucleus and cytoplasm and, in a complex with LMP4, localizes ... More
Focal adhesion size controls tension-dependent recruitment of alpha-smooth muscle actin to stress fibers.
AuthorsGoffin JM, Pittet P, Csucs G, Lussi JW, Meister JJ, Hinz B
JournalJ Cell Biol
PubMed ID16401722
'Expression of alpha-smooth muscle actin (alpha-SMA) renders fibroblasts highly contractile and hallmarks myofibroblast differentiation. We identify alpha-SMA as a mechanosensitive protein that is recruited to stress fibers under high tension. Generation of this threshold tension requires the anchoring of stress fibers at sites of 8-30-microm-long "supermature" focal adhesions (suFAs), which ... More
Age-dependent alterations in the assembly of signal transduction complexes at the site of T cell/APC interaction.
AuthorsTamir A, Eisenbraun MD, Garcia GG, Miller RA
JournalJ Immunol
PubMed ID10903722
'TCR interaction with peptide-MHC complexes triggers migration of protein kinases, actin-binding proteins, and other accessory molecules to the T cell/APC synapse. We used confocal immunofluorescence methods to show that the adapter protein LAT (linker for activation of T cells) and the guanine nucleotide exchange factor Vav also move to the ... More
Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation.
AuthorsHonda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, Kawamoto K, Nakayama K, Morris AJ, Frohman MA, Kanaho Y
JournalCell
PubMed ID10589680
'Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly ... More
Alpha-adducin dissociates from F-actin and spectrin during platelet activation.
AuthorsBarkalow KL, Italiano JE, Chou DE, Matsuoka Y, Bennett V, Hartwig JH
JournalJ Cell Biol
PubMed ID12743105
'Aspectrin-based skeleton uniformly underlies and supports the plasma membrane of the resting platelet, but remodels and centralizes in the activated platelet. alpha-Adducin, a phosphoprotein that forms a ternary complex with F-actin and spectrin, is dephosphorylated and mostly bound to spectrin in the membrane skeleton of the resting platelet at sites ... More
AuthorsSnow CJ, Goody M, Kelly MW, Oster EC, Jones R, Khalil A, Henry CA,
JournalPLoS Genet
PubMed ID18833302
'Skeletal muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction (MTJ). In vertebrates, a great deal is known about muscle specification as well as how somitic cells, as a cohort, generate the early myotome. However, the cellular mechanisms that generate ... More
Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes.
AuthorsKabir N, Schaefer AW, Nakhost A, Sossin WS, Forscher P
JournalJ Cell Biol
PubMed ID11238458
'We describe a novel mechanism for protein kinase C regulation of axonal microtubule invasion of growth cones. Activation of PKC by phorbol esters resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin rich peripheral domain of growth cones, where they are normally excluded. In contrast, inhibition ... More
The Ras/Rac guanine nucleotide exchange factor mammalian Son-of-sevenless interacts with PACSIN 1/syndapin I, a regulator of endocytosis and the actin cytoskeleton.
AuthorsWasiak S, Quinn CC, Ritter B, de Heuvel E, Baranes D, Plomann M, McPherson PS
JournalJ Biol Chem
PubMed ID11352907
'Mammalian Son-of-sevenless (mSos) functions as a guanine nucleotide exchange factor for Ras and Rac, thus regulating signaling to mitogen-activated protein kinases and actin dynamics. In the current study, we have identified a new mSos-binding protein of 50 kDa (p50) that interacts with the mSos1 proline-rich domain. Mass spectrometry analysis and ... More
Osteoclast responses to lipopolysaccharide, parathyroid hormone and bisphosphonates in neonatal murine calvaria analyzed by laser scanning confocal microscopy.
'Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 microg/ml), parathyroid hormone (PTH; 10(-8) M), and bisphosphonates (BPs; 1-25 microM clodronate or 0.1-2.5 microM risedronate) in ... More
Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup.
AuthorsKay JG, Murray RZ, Pagan JK, Stow JL
JournalJ Biol Chem
PubMed ID16513632
'Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor alpha (TNFalpha) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNFalpha is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 4 and SNAP-23. Many functions in immune cells are ... More
Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells.
AuthorsKnowles MK, Guenza MG, Capaldi RA, Marcus AH
JournalProc Natl Acad Sci U S A
PubMed ID12417764
'Subcellular organelle dynamics are strongly influenced by interactions with cytoskeletal filaments and their associated motor proteins, and lead to complex multiexponential relaxations that occur over a wide range of spatial and temporal scales. Here we report spatio-temporal measurements of the fluctuations of the mitochondrial reticulum in osteosarcoma cells by using ... More
Genetic analysis of beta1 integrin "activation motifs" in mice.
AuthorsCzuchra A, Meyer H, Legate KR, Brakebusch C, Fässler R
JournalJ Cell Biol
PubMed ID16954348
'Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin beta cytoplasmic domains. Talin binding disrupts the salt bridge between the alpha/beta tails, leading to tail ... More
ICln, a novel integrin alphaIIbbeta3-associated protein, functionally regulates platelet activation.
AuthorsLarkin D, Murphy D, Reilly DF, Cahill M, Sattler E, Harriott P, Cahill DJ, Moran N
JournalJ Biol Chem
PubMed ID15075326
'A critical role for the conserved alpha-integrin cytoplasmic motif, KVGFFKR, is recognized in the regulation of activation of the platelet integrin alpha(IIb)beta(3). To understand the molecular mechanisms of this regulation, we sought to determine the nature of the protein interactions with this cytoplasmic motif. We used a tagged synthetic peptide, ... More
Actin filaments play a permissive role in the inhibition of store-operated Ca2+ entry by extracellular ATP in rat brown adipocytes.
AuthorsOmatsu-Kanbe M, Shibata M, Yamamoto T, Isono T, Matsuura H
JournalBiochem J
PubMed ID15107014
'Stimulation of P2 receptors with micromolar concentration of ATP evokes a transient increase in [Ca2+]i (intracellular free Ca2+ concentration), primarily due to release of Ca2+ from intracellular stores; such stimulation also triggers almost complete suppression of thapsigargin-evoked sustained [Ca2+]i increase mediated through a store-operated Ca2+ entry pathway in rat brown ... More
A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation.
AuthorsMoss DK, Betin VM, Malesinski SD, Lane JD
JournalJ Cell Sci
PubMed ID16723742
'Dramatic changes in cellular dynamics characterise the apoptotic execution phase, culminating in fragmentation into membrane-bound apoptotic bodies. Previous evidence suggests that actin-myosin plays a dominant role in apoptotic cellular remodelling, whereas all other cytoskeletal elements dismantle. We have used fixed cells and live-cell imaging to confirm that interphase microtubules rapidly ... More
A subset of dynamic actin rearrangements in Drosophila requires the Arp2/3 complex.
AuthorsHudson AM, Cooley L
JournalJ Cell Biol
PubMed ID11854308
'The Arp2/3 complex has been shown to dramatically increase the slow spontaneous rate of actin filament nucleation in vitro, and it is known to be important for remodeling the actin cytoskeleton in vivo. We isolated and characterized loss of function mutations in genes encoding two subunits of the Drosophila Arp2/3 ... More
Effects of surface adsorption on catalytic activity of heavy meromyosin studied using a fluorescent ATP analogue.
AuthorsBalaz M, Sundberg M, Persson M, Kvassman J, Månsson A
JournalBiochemistry
PubMed ID17523677
'Biochemical studies in solution and with myosin motor fragments adsorbed to surfaces (in vitro motility assays) are invaluable for elucidation of actomyosin function. However, there is limited understanding of how surface adsorption affects motor properties, e.g., catalytic activity. Here we address this issue by comparing the catalytic activity of heavy ... More
Multiphoton excitation spectra in biological samples.
AuthorsDickinson ME, Simbuerger E, Zimmermann B, Waters CW, Fraser SE
JournalJ Biomed Opt
PubMed ID12880336
'Multiphoton microscopy is becoming a popular mode of live and fixed cell imaging. This mode of imaging offers several advantages due to the fact that fluorochrome excitation is a nonlinear event resulting in excitation only at the plane of focus. Multiphoton excitation is enhanced by the use of ultrafast lasers ... More
The carboxyl terminus of the alpha-subunit of the amiloride-sensitive epithelial sodium channel binds to F-actin.
AuthorsMazzochi C, Bubien JK, Smith PR, Benos DJ
JournalJ Biol Chem
PubMed ID16356937
'The activity of the amiloride-sensitive epithelial sodium channel (ENaC) is modulated by F-actin. However, it is unknown if there is a direct interaction between alpha-ENaC and actin. We have investigated the hypothesis that the actin cytoskeleton directly binds to the carboxyl terminus of alpha-ENaC using a combination of confocal microscopy, ... More
Altered composition of the immunological synapse in an anergic, age-dependent memory T cell subset.
AuthorsEisenbraun MD, Tamir A, Miller RA
JournalJ Immunol
PubMed ID10843659
'In young mice, memory CD4 T lymphocytes with high P-glycoprotein activity (P-gp(high)) are unresponsive to TCR stimulation in vitro but can be activated by PMA plus ionomycin. The proportion of these hyporesponsive cells increases considerably with age. The earliest events in T cell activation were studied in P-gp(high) and P-gp(low) ... More
Redundant mechanisms recruit actin into the contractile ring in silkworm spermatocytes.
AuthorsChen W, Foss M, Tseng KF, Zhang D,
JournalPLoS Biol
PubMed ID18767903
'Cytokinesis is powered by the contraction of actomyosin filaments within the newly assembled contractile ring. Microtubules are a spindle component that is essential for the induction of cytokinesis. This induction could use central spindle and/or astral microtubules to stimulate cortical contraction around the spindle equator (equatorial stimulation). Alternatively, or in ... More
ECM degradation assays for analyzing local cell invasion.
AuthorsArtym VV, Yamada KM, Mueller SC,
JournalMethods Mol Biol
PubMed ID19247615
'Proteolytic degradation of extracellular matrix (ECM) is a critical step during cell invasion and tissue transmigration that is required for many physiological and pathological processes. Cellular structures that mediate cell adhesion to, degradation of, and invasion into ECM are invadopodia of transformed and tumor cells and podosomes of normal monocytic, ... More
Actin coating of secretory granules during regulated exocytosis correlates with the release of rab3D.
'The present study describes a novel phenomenon in pancreatic acinar cells undergoing regulated exocytosis. When acinar cell preparations were challenged with the secretagogue carbamylcholine, a subpopulation of zymogen granules became coated with filamentous actin. These zymogen granules were always in proximity of the acinar cell apical membrane (the site of ... More
Chemomechanical mapping of ligand-receptor binding kinetics on cells.
AuthorsLee S, Mandic J, Van Vliet KJ
JournalProc Natl Acad Sci U S A
PubMed ID17535923
'The binding kinetics between cell surface receptors and extracellular biomolecules is critical to all intracellular and intercellular activity. Modeling and prediction of receptor-mediated cell functions are facilitated by measurement of the binding properties on whole cells, ideally indicating the subcellular locations or cytoskeletal associations that may affect the function of ... More
Microtubules remodel actomyosin networks in Xenopus egg extracts via two mechanisms of F-actin transport.
'Interactions between microtubules and filamentous actin (F-actin) are crucial for many cellular processes, including cell locomotion and cytokinesis, but are poorly understood. To define the basic principles governing microtubule/F-actin interactions, we used dual-wavelength digital fluorescence and fluorescent speckle microscopy to analyze microtubules and F-actin labeled with spectrally distinct fluorophores in ... More
Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis.
AuthorsBortner CD, Sifre MI, Cidlowski JA,
JournalJ Biol Chem
PubMed ID18187415
'Cell shrinkage, or apoptotic volume decrease (AVD), is a ubiquitous characteristic of programmed cell death that is independent of the death stimulus and occurs in all examples of apoptosis. Here we distinguished two specific stages of AVD based on cell size and a unique early reversal of intracellular ions that ... More
Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors.
AuthorsPikkarainen S, Tokola H, Kerkelä R, Majalahti-Palviainen T, Vuolteenaho O, Ruskoaho H
JournalJ Biol Chem
PubMed ID12446726
'Terminally differentiated cardiac myocytes adapt to mechanical and neurohumoral stress via morphological changes of individual cells accompanied by reactivation of fetal pattern of gene expression. Endothelin-1, a powerful paracrine mediator of myocyte growth, induces similar changes in cultured cardiac myocytes as those seen in hypertrophied heart in vivo. By using ... More
The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis.
AuthorsGnesutta N, Qu J, Minden A
JournalJ Biol Chem
PubMed ID11278822
'The serine/threonine kinase PAK4 was identified first as an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family both in sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response ... More
Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases.
AuthorsReeves PM, Bommarius B, Lebeis S, McNulty S, Christensen J, Swimm A, Chahroudi A, Chavan R, Feinberg MB, Veach D, Bornmann W, Sherman M, Kalman D
JournalNat Med
PubMed ID15980865
'The Poxviridae family members vaccinia and variola virus enter mammalian cells, replicate outside the nucleus and produce virions that travel to the cell surface along microtubules, fuse with the plasma membrane and egress from infected cells toward apposing cells on actin-filled membranous protrusions. We show that cell-associated enveloped virions (CEV) ... More
Mechanistic differences in actin bundling activity of two mammalian formins, FRL1 and mDia2.
AuthorsHarris ES, Rouiller I, Hanein D, Higgs HN
JournalJ Biol Chem
PubMed ID16556604
'Formin proteins are regulators of actin dynamics, mediating assembly of unbranched actin filaments. These multidomain proteins are defined by the presence of a Formin Homology 2 (FH2) domain. Previous work has shown that FH2 domains bind to filament barbed ends and move processively at the barbed end as the filament ... More
Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures.
AuthorsQi W, Ding D, Salvi RJ,
JournalHear Res
PubMed ID18207679
'The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1-6% DMSO for 24h to cochlear organotypic cultures from postnatal day 3 rats and examined ... More
The receptor tyrosine phosphatase CRYPalpha promotes intraretinal axon growth.
AuthorsLedig MM, Haj F, Bixby JL, Stoker AW, Mueller BK
JournalJ Cell Biol
PubMed ID10525542
'Retinal ganglion cell axons grow towards the optic fissure in close contact with the basal membrane, an excellent growth substratum. One of the ligands of receptor tyrosine phosphatase CRYPalpha is located on the retinal and tectal basal membranes. To analyze the role of this RPTP and its ligand in intraretinal ... More
Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase.
AuthorsWahl S, Barth H, Ciossek T, Aktories K, Mueller BK
JournalJ Cell Biol
PubMed ID10769020
'The ephrins, ligands of Eph receptor tyrosine kinases, have been shown to act as repulsive guidance molecules and to induce collapse of neuronal growth cones. For the first time, we show that the ephrin-A5 collapse is mediated by activation of the small GTPase Rho and its downstream effector Rho kinase. ... More
Stabilization of exocytosis by dynamic F-actin coating of zymogen granules in pancreatic acini.
AuthorsNemoto T, Kojima T, Oshima A, Bito H, Kasai H
JournalJ Biol Chem
PubMed ID15184362
'Reorganization of F-actin in the apical region of mouse pancreatic acinar cells during Ca(2+)-dependent exocytosis of zymogen granules was investigated by two-photon excitation microscopy with intact acini. Granules were rapidly coated with F-actin in response to either agonist stimulation or photolysis of a caged-Ca(2+) compound. Such F-actin coating occurred exclusively ... More
Stress fibers are generated by two distinct actin assembly mechanisms in motile cells.
AuthorsHotulainen P, Lappalainen P
JournalJ Cell Biol
PubMed ID16651381
'Stress fibers play a central role in adhesion, motility, and morphogenesis of eukaryotic cells, but the mechanism of how these and other contractile actomyosin structures are generated is not known. By analyzing stress fiber assembly pathways using live cell microscopy, we revealed that these structures are generated by two distinct ... More
Actin restructuring during Salmonella typhimurium infection investigated by confocal and super-resolution microscopy.
AuthorsHan JJ, Kunde YA, Hong-Geller E, Werner JH
Journal
PubMed ID24413454
'We have used super-resolution optical microscopy and confocal microscopy to visualize the cytoskeletal restructuring of HeLa cells that accompanies and enables Salmonella typhimurium internalization. Herein, we report the use of confocal microscopy to verify and explore infection conditions that would be compatible with super-resolution optical microscopy, using Alexa-488 labeled phalloidin ... More
Genetic immunization for antibody generation in research animals by intravenous delivery of plasmid DNA.
'Genetic immunization is an attractive approach to generate antibodies because native proteins are expressed in vivo with normal posttranscriptional modifications, avoiding time-consuming and costly antigen isolation or synthesis. Hydrodynamic tail or limb vein delivery of naked plasmid DNA expression vectors was used to induce antigen-specific antibodies in mice, rats, and ... More
Photoinduced formation of reversible dye radicals and their impact on super-resolution imaging.
Authorsvan de Linde S, Krstic I, Prisner T, Doose S, Heilemann M, Sauer M,
JournalPhotochem Photobiol Sci
PubMed ID21152594
'Radical ions of organic dyes are highly reactive species and have been studied for decades by transient absorption spectroscopy and pulse radiolysis experiments in oxygen-depleted solution. Here we show by continuous wave EPR, absorption, and fluorescence experiments that the triplet state of rhodamine dyes can be photoreduced by thiols to ... More
Cell-to-cell spread and massive vacuole formation after Cryptococcus neoformans infection of murine macrophages.
AuthorsAlvarez M, Casadevall A,
JournalBMC Immunol
PubMed ID17705844
'BACKGROUND: The interaction between macrophages and Cryptococcus neoformans (Cn) is critical for containing dissemination of this pathogenic yeast. However, Cn can either lyse macrophages or escape from within them through a process known as phagosomal extrusion. Both events result in live extracellular yeasts capable of reproducing and disseminating in the ... More
Plakoglobin is required for maintenance of the cortical actin skeleton in early Xenopus embryos and for cdc42-mediated wound healing.
AuthorsKofron M, Heasman J, Lang SA, Wylie CC
JournalJ Cell Biol
PubMed ID12186853
'Early Xenopus embryos are large, and during the egg to gastrula stages, when there is little extracellular matrix, the cytoskeletons of the individual blastomeres are thought to maintain their spherical architecture and provide scaffolding for the cellular movements of gastrulation. We showed previously that depletion of plakoglobin protein during the ... More
Simvastatin suppresses LPS-induced Akt phosphorylation in the human monocyte cell line THP-1.
AuthorsPatel TR, Corbett SA
JournalJ Surg Res
PubMed ID14732356
'BACKGROUND: Activation of the small GTPase, Rac, requires post-translational modification by isoprenylation. Statins interfere with this process by blocking the synthesis of isoprenoid intermediates. The protein kinase Akt is a multifunctional regulator of cell behavior that has been linked to Rac activation. We have shown that lipopolysaccharide (LPS) stimulation leads ... More
Improving signal-to-noise ratio of structured light microscopy based on photon reassignment.
AuthorsSingh VR, Choi H, Yew EY, Bhattacharya D, Yuan L, Sheppard CJ, Rajapakse JC, Barbastathis G, So PT,
JournalBiomed Opt Express
PubMed ID22254180
'In this paper, we report a method for 3D visualization of a biological specimen utilizing a structured light wide-field microscopic imaging system. This method improves on existing structured light imaging modalities by reassigning fluorescence photons generated from off-focal plane excitation, improving in-focus signal strength. Utilizing a maximum likelihood approach, we ... More
Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling.
AuthorsFrischknecht F, Moreau V, Röttger S, Gonfloni S, Reckmann I, Superti-Furga G, Way M
JournalNature
PubMed ID10553910
'Studies of the actin-based motility of the intracellular pathogens Listeria monocytogenes and Shigella flexneri have provided important insight into the events occurring at the leading edges of motile cells. Like the bacteria Listeria and Shigella, vaccinia virus, a relative of the causative agent of smallpox, uses actin-based motility to spread ... More
The doctrine of two schools of thought--a shield or a sword.
AuthorsWeil Z, Gruber D
JournalMed Law
PubMed ID11289640
This paper recognizes that, in medicine at least, there are at least two ways of looking at a problem, be it clinical or legal. The subject is approached from both viewpoints. Emphasis is placed on the background of legal concepts and their application to clinical situations. To illustrate the doctrine, ... More
Induction of de novo subcortical actin filament assembly by Treponema denticola major outer sheath protein.
AuthorsAmin M, Ho AC, Lin JY, Batista da Silva AP, Glogauer M, Ellen RP
JournalInfect Immun
PubMed ID15155678
Treponema denticola and its major outer sheath protein (Msp) induce actin reorganization in fibroblasts. We adapted a barbed-end labeling/imaging assay to monitor Msp-induced subcortical actin filament assembly in neutrophils and fibroblasts. Msp, at an actin-reorganizing concentration, inhibited migration of these dissimilar cell types, whose cytoskeletal functions in locomotion and phagocytosis ... More
'Injecting' yeast.
AuthorsRiveline D, Nurse P,
JournalNat Methods
PubMed ID19503081
Yeast is a powerful genetic model system, but its rigid cell wall has prohibited microinjection. Using microfabricated channels to constrain the fission yeast Schizosaccharomyces pombe, we sheared local regions of individual cells with a piezoelectric unit. The cells remained viable, we detected actin patches in the cell after introduction of ... More
Velocity, processivity, and individual steps of single myosin V molecules in live cells.
AuthorsPierobon P, Achouri S, Courty S, Dunn AR, Spudich JA, Dahan M, Cappello G,
JournalBiophys J
PubMed ID19450497
We report the tracking of single myosin V molecules in their natural environment, the cell. Myosin V molecules, labeled with quantum dots, are introduced into the cytoplasm of living HeLa cells and their motion is recorded at the single molecule level with high spatial and temporal resolution. We perform an ... More
Isolation, structure elucidation and cytotoxic evaluation of endiandrin B from the Australian rainforest plant Endiandra anthropophagorum.
Chemical investigations of the DCM extract from the roots of Endiandra anthropophagorum resulted in the isolation of a new cyclobutane lignan endiandrin B (1), together with the known natural products, endiandrin A (2), and (-)-dihydroguaiaretic acid (3). The structure of 1 was determined by extensive spectroscopic analyses, and confirmed by ... More
Visualising the actin cytoskeleton.
AuthorsSmall J, Rottner K, Hahne P, Anderson KI
JournalMicrosc Res Tech
PubMed ID10506758
The actin cytoskeleton is a dynamic filamentous network whose formation and remodeling underlies the fundamental processes of cell motility and shape determination. To serve these roles, different compartments of the actin cytoskeleton engage in forming specific coupling sites between neighbouring cells and with the underlying matrix, which themselves serve signal ... More
p24 proteins and quality control of LIN-12 and GLP-1 trafficking in Caenorhabditis elegans.
AuthorsWen C, Greenwald I
JournalJ Cell Biol
PubMed ID10366590
Mutations in the Caenorhabditis elegans sel-9 gene elevate the activity of lin-12 and glp-1, which encode members of the LIN-12/NOTCH family of receptors. Sequence analysis indicates SEL-9 is one of several C. elegans p24 proteins. Allele-specific genetic interactions suggest that reducing sel-9 activity increases the activity of mutations altering the ... More
ARAP1: a point of convergence for Arf and Rho signaling.
AuthorsMiura K, Jacques KM, Stauffer S, Kubosaki A, Zhu K, Hirsch DS, Resau J, Zheng Y, Randazzo PA
JournalMol Cell
PubMed ID11804590
We have identified ARAP1 and ARAP2 and examined ARAP1 as a possible link between phosphoinositide-, Arf-, and Rho-mediated cell signaling. ARAP1 contains Arf GAP, Rho GAP, Ankyrin repeat, Ras-associating, and five PH domains. In vitro, ARAP1 had Rho GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent Arf GAP activity. ARAP1 associated with ... More
Light-induced dark states of organic fluochromes enable 30 nm resolution imaging in standard media.
We show that high quantum efficiency fluorophores can exhibit reversible photobleaching. This observation provides the basis for an imaging technique we call reversible photobleaching microscopy. We demonstrate applicability of this technique using antibody labeled biological samples in standard aqueous (or glycerol based) media to produce far-field images at approximately 30 ... More
Optimal processing method to obtain four-color confocal fluorescent images of the cytoskeleton and nucleus in three-dimensional chondrocyte cultures.
AuthorsBlanc A, Tran-Khanh N, Filion D, Buschmann MD
JournalJ Histochem Cytochem
PubMed ID15933071
Tissue engineering of articular cartilage requires accurate imaging of the chondrocyte cytoskeleton. Past studies have applied various fixation and permeabilization protocols without optimization of parameters. In this study, we have examined procedures using glutaraldehyde and paraformaldehyde as fixatives and Triton X-100 and Octyl-POE as permeabilizing detergents. A four-color fluorescence confocal ... More
Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
AuthorsTanoue T, Takeichi M
JournalJ Cell Biol
PubMed ID15148305
Fat cadherins form a distinct subfamily of the cadherin gene superfamily, and are featured by their unusually large extracellular domain. In this work, we investigated the function of a mammalian Fat cadherin. Fat1 was localized at filopodial tips, lamellipodial edges, and cell-cell boundaries, overlapping with dynamic actin structures. RNA interference-mediated ... More
Paper-supported 3D cell culture for tissue-based bioassays.
AuthorsDerda R, Laromaine A, Mammoto A, Tang SK, Mammoto T, Ingber DE, Whitesides GM,
JournalProc Natl Acad Sci U S A
PubMed ID19846768
Fundamental investigations of human biology, and the development of therapeutics, commonly rely on 2D cell-culture systems that do not accurately recapitulate the structure, function, or physiology of living tissues. Systems for 3D cultures exist but do not replicate the spatial distributions of oxygen, metabolites, and signaling molecules found in tissues. ... More
Immature CD4+CD8+ thymocytes do not polarize lipid rafts in response to TCR-mediated signals.
AuthorsEbert PJ, Baker JF, Punt JA
JournalJ Immunol
PubMed ID11067895
TCR-mediated stimulation induces activation and proliferation of mature T cells. When accompanied by signals through the costimulatory receptor CD28, TCR signals also result in the recruitment of cholesterol- and glycosphingolipid-rich membrane microdomains (lipid rafts), which are known to contain several molecules important for T cell signaling. Interestingly, immature CD4(+)CD8(+) thymocytes ... More
Targeting of calcium:calmodulin signals to the cytoskeleton by IQGAP1.
AuthorsPsatha MI, Razi M, Koffer A, Moss SE, Sacks DB, Bolsover SR
JournalCell Calcium
PubMed ID17137623
Mast cells reorganize their actin cytoskeleton in response to cytosolic calcium signals while in parallel secreting histamine and other inflammatory mediators. The effect of calcium on actin is mediated in large part through calmodulin. EGFP-tagged calmodulin is concentrated in the actin-rich cortex of RBL-2H3 mast cells. Transfection with small interfering ... More
Arp2/3 complex and actin dynamics are required for actin-based mitochondrial motility in yeast.
AuthorsBoldogh IR, Yang HC, Nowakowski WD, Karmon SL, Hays LG, Yates JR, Pon LA
JournalProc Natl Acad Sci U S A
PubMed ID11248049
The Arp2/3 complex is implicated in actin polymerization-driven movement of Listeria monocytogenes. Here, we find that Arp2p and Arc15p, two subunits of this complex, show tight, actin-independent association with isolated yeast mitochondria. Arp2p colocalizes with mitochondria. Consistent with this result, we detect Arp2p-dependent formation of actin clouds around mitochondria in ... More
Fluorescence lifetime of actin in the familial hypertrophic cardiomyopathy transgenic heart.
Clinical studies have revealed that the D166V mutation in the ventricular myosin regulatory light chain (RLC) can cause a malignant phenotype of familial hypertrophic cardiomyopathy (FHC). It has been proposed that RLC induced FHC in the heart originates at the level of the myosin cross-bridge due to alterations in the ... More
Actin reorganization is required for the formation of polarized B cell receptor signalosomes in response to both soluble and membrane-associated antigens.
AuthorsLiu C, Miller H, Orlowski G, Hang H, Upadhyaya A, Song W,
JournalJ Immunol
PubMed ID22387556
B cells encounter both soluble Ag (sAg) and membrane-associated Ag (mAg) in the secondary lymphoid tissue, yet how the physical form of Ag modulates B cell activation remains unclear. This study compares actin reorganization and its role in BCR signalosome formation in mAg- and sAg-stimulated B cells. Both mAg and ... More
A balance of Bruton's tyrosine kinase and SHIP activation regulates B cell receptor cluster formation by controlling actin remodeling.
AuthorsLiu C, Miller H, Hui KL, Grooman B, Bolland S, Upadhyaya A, Song W,
JournalJ Immunol
PubMed ID21622861
The activation of the BCR, which initiates B cell activation, is triggered by Ag-induced self-aggregation and clustering of receptors at the cell surface. Although Ag-induced actin reorganization is known to be involved in BCR clustering in response to membrane-associated Ag, the underlying mechanism that links actin reorganization to BCR activation ... More
Quantifying retinal nerve fiber layer thickness in whole-mounted retina.
AuthorsHuang XR, Knighton RW, Shestopalov V,
JournalExp Eye Res
PubMed ID16828473
In order to relate optical measurement of the retinal nerve fiber layer (RNFL) to the underlying structure, one must have accurate values for RNFL thickness at the locations measured optically. The purpose of this study was to develop a method for measuring RNFL thickness at any location on retinal tissue ... More
Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila.
AuthorsKöppen M, Fernández BG, Carvalho L, Jacinto A, Heisenberg CP,
JournalDevelopment
PubMed ID16794032
Epithelial morphogenesis depends on coordinated changes in cell shape, a process that is still poorly understood. During zebrafish epiboly and Drosophila dorsal closure, cell-shape changes at the epithelial margin are of critical importance. Here evidence is provided for a conserved mechanism of local actin and myosin 2 recruitment during theses ... More
Familial hypertrophic cardiomyopathy can be characterized by a specific pattern of orientation fluctuations of actin molecules .
AuthorsBorejdo J, Szczesna-Cordary D, Muthu P, Calander N,
JournalBiochemistry
PubMed ID20509708
A single-point mutation in the gene encoding the ventricular myosin regulatory light chain (RLC) is sufficient to cause familial hypertrophic cardiomyopathy (FHC). Most likely, the underlying cause of this disease is an inefficient energy utilization by the mutated cardiac muscle. We set out to devise a simple method to characterize ... More
Three-dimensional structured illumination microscopy of liver sinusoidal endothelial cell fenestrations.
Fenestrations are pores in liver sinusoidal endothelial cells that filter substrates and debris between the blood and hepatocytes. Fenestrations have significant roles in aging and the regulation of lipoproteins. However their small size (<200 nm) has prohibited any functional analysis by light microscopy. We employed structured illumination light microscopy to ... More
Recognition, presence, and survival of locust central nervous glia in situ and in vitro.
AuthorsGocht D, Wagner S, Heinrich R,
JournalMicrosc Res Tech
PubMed ID19115332
Insect glial cells serve functions for the formation, maintenance, and performance of the central nervous system in ways similar to their vertebrate counterparts. Characterization of physiological mechanisms that underlie the roles of glia in invertebrates is largely incomplete, partly due to the lack of markers that universally label all types ... More
p53-cofactor JMY is a multifunctional actin nucleation factor.
Many cellular structures are assembled from networks of actin filaments, and the architecture of these networks depends on the mechanism by which the filaments are formed. Several classes of proteins are known to assemble new filaments, including the Arp2/3 complex, which creates branched filament networks, and Spire, which creates unbranched ... More
4D super-resolution microscopy with conventional fluorophores and single wavelength excitation in optically thick cells and tissues.
Optical super-resolution imaging of fluorescently stained biological samples is rapidly becoming an important tool to investigate protein distribution at the molecular scale. It is therefore important to develop practical super-resolution methods that allow capturing the full three-dimensional nature of biological systems and also can visualize multiple protein species in the ... More
Single-step process to reconstitute cell membranes on solid supports.
AuthorsMager MD, Melosh NA,
JournalLangmuir
PubMed ID20205459
A new technique is presented to create supported lipid bilayers from whole cell lipids without the use of detergent or solvent extraction. In a modification of the bubble collapse deposition (BCD) technique, an air bubble is created underwater and brought into contact with a population of cells. The high-energy air/water ... More
A human CXCL13-induced actin polymerization assay measured by fluorescence plate reader.
AuthorsAlley J, Bloom L, Kasaian M, Gao H, Berstein G, Clark JD, Miao W,
JournalAssay Drug Dev Technol
PubMed ID20085454
The chemokine receptor CXCR5 is predominantly expressed on mature B cells and follicular T-helper cells. CXCR5 and its ligand CXCL13 participate in ectopic germinal center formation at the inflammatory sites of multiple immune diseases such as rheumatoid arthritis, multiple sclerosis, and Sjogren's syndrome. Therefore, disrupting CXCL13-induced chemotaxis may be a ... More
Redistribution of actin during assembly and reassembly of the contractile ring in grasshopper spermatocytes.
AuthorsAlsop GB, Chen W, Foss M, Tseng KF, Zhang D,
JournalPLoS One
PubMed ID19287500
Cytokinesis in animal cells requires the assembly of an actomyosin contractile ring to cleave the cell. The ring is highly dynamic; it assembles and disassembles during each cell cleavage, resulting in the recurrent redistribution of actin. To investigate this process in grasshopper spermatocytes, we mechanically manipulated the spindle to induce ... More
Stimulus-dependent regulation of the phagocyte NADPH oxidase by a VAV1, Rac1, and PAK1 signaling axis.
AuthorsRoepstorff K, Rasmussen I, Sawada M, Cudre-Maroux C, Salmon P, Bokoch G, van Deurs B, Vilhardt F,
JournalJ Biol Chem
PubMed ID18160398
The p21-activated kinase-1 (PAK1) is best known for its role in the regulation of cytoskeletal and transcriptional signaling pathways. We show here in the microglia cell line Ra2 that PAK1 regulates NADPH oxidase (NOX-2) activity in a stimulus-specific manner. Thus, conditional expression of PAK1 dominant-positive mutants enhanced, whereas dominant-negative mutants ... More
Histamine-induced actin polymerization in human eosinophils: an imaging approach for histamine H4 receptor.
AuthorsBarnard R, Barnard A, Salmon G, Liu W, Sreckovic S,
JournalCytometry A
PubMed ID18163465
Image-based screening, a new and flexible tool in the drug discovery cascade, is amenable to many different targets. This article describes a particular use of the Cellomics ArrayScan in developing a functional screen for histamine H(4) receptor (H(4)R) antagonists that have potential utility in inflammatory diseases of the airways such ... More
Amplification of PVT1 contributes to the pathophysiology of ovarian and breast cancer.
AuthorsGuan Y, Kuo WL, Stilwell JL, Takano H, Lapuk AV, Fridlyand J, Mao JH, Yu M, Miller MA, Santos JL, Kalloger SE, Carlson JW, Ginzinger DG, Celniker SE, Mills GB, Huntsman DG, Gray JW,
JournalClin Cancer Res
PubMed ID17908964
This study was designed to elucidate the role of amplification at 8q24 in the pathophysiology of ovarian and breast cancer because increased copy number at this locus is one of the most frequent genomic abnormalities in these cancers. To accomplish this, we assessed the association of amplification at 8q24 with ... More
Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis.
Dendritic spines are small protrusions along dendrites where the postsynaptic components of most excitatory synapses reside in the mature brain. Morphological changes in these actin-rich structures are associated with learning and memory formation. Despite the pivotal role of the actin cytoskeleton in spine morphogenesis, little is known about the mechanisms ... More
Expression levels of a kinesin-13 microtubule depolymerase modulates the effectiveness of anti-microtubule agents.
AuthorsSchimizzi GV, Currie JD, Rogers SL,
JournalPLoS One
PubMed ID20614032
Chemotherapeutic drugs often target the microtubule cytoskeleton as a means to disrupt cancer cell mitosis and proliferation. Anti-microtubule drugs inhibit microtubule dynamics, thereby triggering apoptosis when dividing cells activate the mitotic checkpoint. Microtubule dynamics are regulated by microtubule-associated proteins (MAPs); however, we lack a comprehensive understanding about how anti-microtubule agents ... More
Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties.
AuthorsLevina V, Marrangoni AM, DeMarco R, Gorelik E, Lokshin AE,
JournalPLoS One
PubMed ID18728788
Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce ... More
AuthorsColvin RA, Means TK, Diefenbach TJ, Moita LF, Friday RP, Sever S, Campanella GS, Abrazinski T, Manice LA, Moita C, Andrews NW, Wu D, Hacohen N, Luster AD,
JournalNat Immunol
PubMed ID20473299
Chemokines and other chemoattractants direct leukocyte migration and are essential for the development and delivery of immune and inflammatory responses. To probe the molecular mechanisms that underlie chemoattractant-guided migration, we did an RNA-mediated interference screen that identified several members of the synaptotagmin family of calcium-sensing vesicle-fusion proteins as mediators of ... More