Abstract：
:Clathrin heavy chain is the structural component of the clathrin triskelion, but unique functions for the two distinct and highly conserved clathrin light chains (CLCa and CLCb, also known as CLTA and CLTB, respectively) have been elusive. Here, we show that following detachment and replating, CLCa is uniquely responsible for promoting efficient cell spreading and migration. Selective depletion of CLCa, but not of CLCb, reduced the initial phase of isotropic spreading of HeLa, H1299 and HEK293 cells by 60-80% compared to siRNA controls, and wound closure and motility by ∼50%. Surface levels of β1-integrins were unaffected by CLCa depletion. However, CLCa was required for effective targeting of FAK (also known as PTK2) and paxillin to the adherent surface of spreading cells, for integrin-mediated activation of Src, FAK and paxillin, and for maturation of focal adhesions, but not their microtubule-based turnover. Depletion of CLCa also blocked the interaction of clathrin with the nucleation-promoting factor WAVE complex, and altered actin distribution. Furthermore, preferential recruitment of CLCa to budding protrusions was also observed. These results comprise the first identification of CLCa-specific functions, with implications for normal and neoplastic integrin-based signaling and cell migration.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Tsygankova OM,Keen JHdoi
10.1242/jcs.224030subject
Has Abstractpub_date
2019-05-15 00:00:00issue
10eissn
0021-9533issn
1477-9137pii
jcs.224030journal_volume
132pub_type
杂志文章abstract：:The extracellular signal-regulated protein kinase ERK1/2 is a crucial effector linking extracellular stimuli to cellular responses: upon phosphorylation ERK [also known as mitogen-activated protein kinase P42/P44 (MAPK)] concentrates in the nucleus where it activates specific programs of gene expression. Notwithstandi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03272
更新日期：2006-12-01 00:00:00
abstract：:A number of structural and functional subnuclear compartments have been described, including regions exclusive of chromosomes previously hypothesized to form a reactive nuclear space. We have now explored this accessible nuclear space and interchromosomal nucleoplasmic domains experimentally using Xenopus vimentin eng...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:HT-29 cells selected by adaptation to 10(-5) M methotrexate (HT-29 MTX) are a homogeneous cell population producing high amounts of mucin. Intracellular mucins and proteoglycans were isolated from these cells by ultracentrifugation of cell lysates on a cesium bromide gradient and further separated by anion-exchange hi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:The novel concept of a centrosomal anchoring complex, which is distinct from the gamma-tubulin nucleating complex, has previously been proposed following studies on cochlear epithelial cells. In this investigation we present evidence from two different cell systems which suggests that the centrosomal protein ninein is...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:Desmocollin 3 (Dsc3) is a transmembrane glycoprotein that belongs to the cadherin family of cell adhesion receptors. Together with desmoglein(s), it forms the transmembrane core of desmosomes, a multiprotein complex involved in cell adhesion, organization of the cytoskeleton, cell sorting and cell signaling. Previous ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02769
更新日期：2006-02-01 00:00:00
abstract：:Eukaryotic cell cycles are controlled by the activities of cyclin-dependent kinases (cdks). The major cdk in budding yeast, Saccharomyces cerevisiae, is Cdc28p. Activation of Cdc28p requires phosphorylation on threonine 169 and binding to a cyclin. Thr-169 is phosphorylated by the cdk-activating kinase (CAK), Cak1p, w...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-12-18 00:00:00
abstract：:Crosstalk between the microtubule (MT) and actin cytoskeletons is fundamental to many cellular processes including cell polarisation and cell motility. Previous work has shown that members of the growth-arrest-specific 2 (GAS2) family mediate the crosstalk between filamentous actin (F-actin) and MTs, but the molecular...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.140558
更新日期：2014-06-15 00:00:00
abstract：:Skeletal and heart muscle-specific variant of the α subunit of nascent polypeptide associated complex (skNAC; encoded by NACA) is exclusively found in striated muscle cells. Its function, however, is largely unknown. Previous reports have demonstrated that skNAC binds to m-Bop/Smyd1, a multi-functional protein that re...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.150334
更新日期：2014-09-01 00:00:00
abstract：:Focal adhesions are complex multi-molecular structures that link the actin cytoskeleton to the extracellular matrix through integrin adhesion receptors and play a key role in regulation of many cellular functions. LAR (also known as PTPRF) is a receptor protein tyrosine phosphatase that regulates PDGF signalling and l...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.191379
更新日期：2016-08-01 00:00:00
abstract：:Prox1 plays pivotal roles during embryonic lymphatic development and maintenance of adult lymphatic systems by modulating the expression of various lymphatic endothelial cell (LEC) markers, such as vascular endothelial growth factor receptor 3 (VEGFR3). However, the molecular mechanisms by which Prox1 transactivates i...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.083998
更新日期：2011-08-15 00:00:00
abstract：:Maintenance of epithelial polarity depends on the correct localization and levels of polarity determinants. The evolutionarily conserved transmembrane protein Crumbs is crucial for the size and identity of the apical membrane, yet little is known about the molecular mechanisms controlling the amount of Crumbs at the s...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.174573
更新日期：2015-12-15 00:00:00
abstract：:Regulation of the localization of mRNAs and local translation are universal features in eukaryotes and contribute to cellular asymmetry and differentiation. In Saccharomyces cerevisiae, localization of mRNAs that encode membrane proteins requires the She protein machinery, including the RNA-binding protein She2p, as w...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.149799
更新日期：2014-08-01 00:00:00
abstract：:The coordinated trafficking and tethering of membrane cargo within cells relies on the function of distinct cytoskeletal motors that are targeted to specific subcellular compartments through interactions with protein adaptors and phospholipids. The unique actin motor myosin VI functions at distinct steps during clathr...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.095554
更新日期：2013-06-15 00:00:00
abstract：:It is now becoming clear that additional transmembrane components can modify integrin-mediated adhesion. Syndecan-4 is a transmembrane heparan sulfate proteoglycan whose external glycosaminoglycan chains can bind extracellular matrix ligands and whose core protein cytoplasmic domain can signal during adhesion. Two pap...
journal_title：Journal of cell science
pub_type： 评论,杂志文章,评审
doi：
更新日期：1999-10-01 00:00:00
abstract：:The recently identified 63 kDa membrane protein, p63, is a resident protein of a membrane network interposed in between rough ER and Golgi apparatus. To characterize p63 at the molecular level a 2.91 kb cDNA encoding p63 has been isolated from a human placenta lambda gt10 cDNA library. Sequence analysis of tryptic pep...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:In previous work we have shown that ovarian hormones, when injected into ovariectomized rats, alter the fine structure of the plasma membrane of endometrial epithelial cells. In this paper freeze-fractures have been used to study the apical plasma membrane of endometrial epithelial cells of rats during the period of b...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-06-01 00:00:00
abstract：:The structural events in the stigma and transmitting tissue of Petunia hybrida pistils that accompany compatible and incompatible intraspecific pollinations have been investigated in detail, together with the changes in reserve levels that also take place at this time. Many of these phenomena may be explained in terms...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-04-01 00:00:00
abstract：:Recent evidence suggests that organization of the extracellular matrix (ECM) into aligned fibrils or fibril-like ECM topographies promotes rapid migration in fibroblasts. However, the mechanisms of cell migration that are altered by these changes in micro-environmental topography remain unknown. Here, using 1D fibrill...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.098806
更新日期：2012-05-01 00:00:00
abstract：:The monoclonal antibody AGF2.3 identifies a nuclear envelope protein that is restricted to certain cell types. In particular, this antigen shows a reduced level of expression during haemopoietic cell maturation. In this study, we have examined the relationship of this protein to known nuclear envelope proteins that ha...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:The movement of cells in small groups, or clusters, was studied in vitro using epithelioid cells from Gordon-Kosswig melanomas (from poecelid fish) and time-lapse cinemicrography. Tumour explants cultured on glass yield cell sheets from which groups of cells separate and become independently motile clusters. These clu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-06-01 00:00:00
abstract：:Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved mRNA surveillance system that degrades mRNA transcripts that harbour a premature translation-termination codon (PTC), thus reducing the synthesis of truncated proteins that would otherwise have deleterious effects. Although extensive research has identi...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.120220
更新日期：2013-06-15 00:00:00
abstract：:Vertebrate tropomyosins (TMs) are expressed from four genes, and at least 18 distinct isoforms are generated via a complex pattern of alternative RNA splicing and alternative promoters. The functional significance of this isoform diversity is largely unknown and it remains to be determined whether specific isoforms ar...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:Ligand-dependent nuclear import is crucial for the function of the androgen receptor (AR) in both health and disease. The unliganded AR is retained in the cytoplasm but, on binding 5alpha-dihydrotestosterone, it translocates into the nucleus and alters transcription of its target genes. Nuclear import of AR is mediate...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.022103
更新日期：2008-04-01 00:00:00
abstract：:After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and ca...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03386
更新日期：2007-03-01 00:00:00
abstract：:Expression of a dominant negative fragment of the spectrin family member Syne-1 causes an accumulation of binucleate cells, suggesting a role for this protein in cytokinesis. An association of this fragment with the C-terminal tail domain of the kinesin II subunit KIF3B was identified by yeast two-hybrid and co-precip...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00892
更新日期：2004-02-01 00:00:00
abstract：:Molecular mechanisms of chemotactic response are highly conserved among many eukaryotic cells including human leukocytes and Dictyostelium discoideum cells. The cells can sense the differences in chemoattractant concentration across the cell body and respond by extending pseudopods from the cell side facing to a highe...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02824
更新日期：2006-03-15 00:00:00
abstract：:The PX domain, which until recently was an orphan domain, has emerged as the latest member of the phosphoinositide-binding module superfamily. Structural studies have revealed that it has a novel fold and identified key residues that interact with the bound phosphoinositide, enabling some prediction of phosphoinositid...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：
更新日期：2002-03-15 00:00:00
abstract：:Endothelial cells are known to undergo transitions in cell shape during long-term culture. Thus, the assumption that the separate phenotypes of microvascular endothelial cells (MVEC) recently isolated from bovine corpus luteum represent constitutively different cell strains cannot automatically be made. For this reaso...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:The Arabidopsis thaliana ASY1 gene is essential for homologous chromosome synapsis. Antibodies specific to Asy1 protein and its homologue BoAsy1 from the related crop species Brassica oleracea have been used to investigate the temporal expression and localization of the protein in both species. Asy1 is initially detec...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00048
更新日期：2002-09-15 00:00:00
abstract：:RAS isoforms have been proposed to exhibit differing biological outputs due to differences in their relative occupancy of cellular organelles and signalling microdomains. The membrane binding and targeting motifs of RAS are encoded by the C-terminal hypervariable region (HVR), and the precise localisation depends upon...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.020107
更新日期：2008-02-15 00:00:00
