clathrin heavy chains


Summary: The heavy chain subunits of clathrin.

Top Publications

  1. Wettey F, Hawkins S, Stewart A, Luzio J, Howard J, Jackson A. Controlled elimination of clathrin heavy-chain expression in DT40 lymphocytes. Science. 2002;297:1521-5 pubmed
    ..Surprisingly, clathrin removal did not affect the morphology or biochemical composition of lysosomes. ..
  2. Wingen C, Stümpges B, Hoch M, Behr M. Expression and localization of clathrin heavy chain in Drosophila melanogaster. Gene Expr Patterns. 2009;9:549-54 pubmed publisher
    ..Together, the antibody may serve as a new tool to study the function of Chc in clathrin-dependent cellular processes, such as endocytosis. ..
  3. Enari M, Ohmori K, Kitabayashi I, Taya Y. Requirement of clathrin heavy chain for p53-mediated transcription. Genes Dev. 2006;20:1087-99 pubmed
    ..Thus, nuclear CHC is required for the transactivation of p53 target genes and plays a distinct role from clathrin-mediated endocytosis. ..
  4. Wakeham D, Abi Rached L, Towler M, Wilbur J, Parham P, Brodsky F. Clathrin heavy and light chain isoforms originated by independent mechanisms of gene duplication during chordate evolution. Proc Natl Acad Sci U S A. 2005;102:7209-14 pubmed
    ..Thus, independent mechanisms of gene duplication expanded clathrin functions, concomitant with development of neuromuscular sophistication in chordates...
  5. Sirotkin H, Morrow B, Dasgupta R, Goldberg R, Patanjali S, Shi G, et al. Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome. Hum Mol Genet. 1996;5:617-24 pubmed
    ..Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes. ..
  6. Sato K, Ernstrom G, Watanabe S, Weimer R, Chen C, Sato M, et al. Differential requirements for clathrin in receptor-mediated endocytosis and maintenance of synaptic vesicle pools. Proc Natl Acad Sci U S A. 2009;106:1139-44 pubmed publisher
    ..Taken together, these results indicate that a high level of CHC activity is required for receptor-mediated endocytosis in nonneuronal cells but is largely dispensable for maintenance of synaptic vesicle pools. ..
  7. Newpher T, Idrissi F, Geli M, Lemmon S. Novel function of clathrin light chain in promoting endocytic vesicle formation. Mol Biol Cell. 2006;17:4343-52 pubmed
    ..We propose that LC binding to Sla2p positively regulates Sla2p for efficient endocytic vesicle formation...
  8. Fu W, Tao W, Zheng P, Fu J, Bian M, Jiang Q, et al. Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment. J Cell Sci. 2010;123:3645-51 pubmed publisher
    ..Together, these results indicate that the recruitment of phosphorylated TACC3 to spindle poles by CHC ensures proper spindle assembly and chromosome alignment, and is regulated by Ran. ..
  9. Pishvaee B, Munn A, Payne G. A novel structural model for regulation of clathrin function. EMBO J. 1997;16:2227-39 pubmed
    ..On the basis of this conclusion, we propose a new model for the organization of the triskelion vertex which provides a structural basis for regulatory effects of Clc on clathrin function. ..

More Information


  1. Deborde S, Perret E, Gravotta D, Deora A, Salvarezza S, Schreiner R, et al. Clathrin is a key regulator of basolateral polarity. Nature. 2008;452:719-23 pubmed publisher
    ..Our results demonstrate a broad requirement for clathrin in basolateral protein trafficking in epithelial cells...
  2. Tahara H, Yokota E, Igarashi H, Orii H, Yao M, Sonobe S, et al. Clathrin is involved in organization of mitotic spindle and phragmoplast as well as in endocytosis in tobacco cell cultures. Protoplasma. 2007;230:1-11 pubmed
    ..These data strongly suggest that clathrin is intimately involved in the formation of the spindle and phragmoplast, as well as in endocytosis. ..
  3. Kedra D, Peyrard M, Fransson I, Collins J, Dunham I, Roe B, et al. Characterization of a second human clathrin heavy chain polypeptide gene (CLH-22) from chromosome 22q11. Hum Mol Genet. 1996;5:625-31 pubmed
    ..Our Northern and Southern blot analyses of meningiomas clearly suggest the CLH-22 gene may be involved in the tumor development and can be considered as a candidate for a tumor suppressor. ..
  4. Chen C, Graham T. An arf1Delta synthetic lethal screen identifies a new clathrin heavy chain conditional allele that perturbs vacuolar protein transport in Saccharomyces cerevisiae. Genetics. 1998;150:577-89 pubmed
  5. Girard M, Allaire P, McPherson P, Blondeau F. Non-stoichiometric relationship between clathrin heavy and light chains revealed by quantitative comparative proteomics of clathrin-coated vesicles from brain and liver. Mol Cell Proteomics. 2005;4:1145-54 pubmed
  6. Chen C, Brodsky F. Huntingtin-interacting protein 1 (Hip1) and Hip1-related protein (Hip1R) bind the conserved sequence of clathrin light chains and thereby influence clathrin assembly in vitro and actin distribution in vivo. J Biol Chem. 2005;280:6109-17 pubmed
    ..Together these results suggest that the roles of Hip1 and Hip1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chains. ..
  7. Towler M, Gleeson P, Hoshino S, Rahkila P, Manalo V, Ohkoshi N, et al. Clathrin isoform CHC22, a component of neuromuscular and myotendinous junctions, binds sorting nexin 5 and has increased expression during myogenesis and muscle regeneration. Mol Biol Cell. 2004;15:3181-95 pubmed
    ..These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions. ..
  8. Royle S, Bright N, Lagnado L. Clathrin is required for the function of the mitotic spindle. Nature. 2005;434:1152-7 pubmed
    ..The importance of clathrin for normal mitosis may be relevant to understanding human cancers that involve gene fusions of clathrin heavy chain. ..
  9. Vassilopoulos S, Esk C, Hoshino S, Funke B, Chen C, Plocik A, et al. A role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism. Science. 2009;324:1192-6 pubmed publisher
    ..Thus, CHC22-dependent membrane trafficking constitutes a species-restricted pathway in human muscle and fat with potential implications for type 2 diabetes. ..
  10. Hinrichsen L, Harborth J, Andrees L, Weber K, Ungewickell E. Effect of clathrin heavy chain- and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells. J Biol Chem. 2003;278:45160-70 pubmed
    ..Since neither clathrin nor AP-2 is essential for the internalization of EGF, we conclude that it is taken up by an alternative mechanism. ..
  11. Royle S, Lagnado L. Trimerisation is important for the function of clathrin at the mitotic spindle. J Cell Sci. 2006;119:4071-8 pubmed
  12. Radulescu A, Shields D. Clathrin is required for postmitotic Golgi reassembly. FASEB J. 2012;26:129-36 pubmed publisher
    ..Our findings build on previous independent reports that clathrin is required for Golgi reassembly following disruption with pharmacological agents and for mitotic chromosome congression. ..
  13. Radulescu A, Siddhanta A, Shields D. A role for clathrin in reassembly of the Golgi apparatus. Mol Biol Cell. 2007;18:94-105 pubmed
  14. Adam T, Bouhidel K, Der C, Robert F, Najid A, Simon Plas F, et al. Constitutive expression of clathrin hub hinders elicitor-induced clathrin-mediated endocytosis and defense gene expression in plant cells. FEBS Lett. 2012;586:3293-8 pubmed publisher
    ..Such an inhibition has no impact on early events in the cryptogein signaling pathway but reduces the expression of defense-associated genes...
  15. Venken K, Kasprowicz J, Kuenen S, Yan J, Hassan B, Verstreken P. Recombineering-mediated tagging of Drosophila genomic constructs for in vivo localization and acute protein inactivation. Nucleic Acids Res. 2008;36:e114 pubmed publisher
    ..Our tagging technology is efficient and versatile, adaptable to any tag desired and paves the way to genome-wide gene tagging in Drosophila. ..
  16. Young A. Structural insights into the clathrin coat. Semin Cell Dev Biol. 2007;18:448-58 pubmed
    ..In this review I outline the roles of clathrin within the cell and the recent structural advances that have improved our understanding of clathrin-clathrin and clathrin-protein interactions. ..
  17. Hood F, Royle S. Functional equivalence of the clathrin heavy chains CHC17 and CHC22 in endocytosis and mitosis. J Cell Sci. 2009;122:2185-90 pubmed publisher
    Clathrin is crucial for endocytosis and plays a recently described role in mitosis. Two clathrin heavy chains (CHCs) are found in humans: the ubiquitous CHC17, and CHC22, a CHC that is enriched in skeletal muscle...
  18. Esk C, Chen C, Johannes L, Brodsky F. The clathrin heavy chain isoform CHC22 functions in a novel endosomal sorting step. J Cell Biol. 2010;188:131-44 pubmed publisher
    ..Like CHC22, syntaxin 10 is not expressed in mice but is present in humans and other vertebrates, implicating two species-restricted endosomal traffic proteins in GLUT4 transport. ..
  19. Lin C, Hu C, Shih H. Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability. J Cell Biol. 2010;189:1097-105 pubmed publisher
    ..Our findings elucidate the association between aurora A phosphorylation and spindle apparatus and demonstrate that regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles. ..
  20. Blackbourn H, Jackson A. Plant clathrin heavy chain: sequence analysis and restricted localisation in growing pollen tubes. J Cell Sci. 1996;109 ( Pt 4):777-86 pubmed
  21. Rapoport I, Boll W, Yu A, Böcking T, Kirchhausen T. A motif in the clathrin heavy chain required for the Hsc70/auxilin uncoating reaction. Mol Biol Cell. 2008;19:405-13 pubmed
    ..Thus, the QLMLT motif is required for Hsc-70-facilitated uncoating, consistent with the proposal that this sequence is a specific target of the chaperone...
  22. Neumann Staubitz P, Hall S, Kuo J, Jackson A. Characterization of a temperature-sensitive vertebrate clathrin heavy chain mutant as a tool to study clathrin-dependent events in vivo. PLoS ONE. 2010;5:e12017 pubmed publisher
    ..Fourthly, in contrast to yeast, actin does not appear to actively compensate in general endocytosis. Thus, there seem to be differences between vertebrates and yeast which can be studied in further detail with this newly created tool. ..
  23. Ganeff C, Remouchamps C, Boutaffala L, Bénézech C, Galopin G, Vandepaer S, et al. Induction of the alternative NF-?B pathway by lymphotoxin ?? (LT??) relies on internalization of LT? receptor. Mol Cell Biol. 2011;31:4319-34 pubmed publisher
    ..Thus, our data shed light on LT?R cellular trafficking as a process required for specific biological functions of NF-?B. ..
  24. Kim M, Sorg I, Arrieumerlou C. Endocytosis-independent function of clathrin heavy chain in the control of basal NF-?B activation. PLoS ONE. 2011;6:e17158 pubmed publisher
    ..Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer. ..
  25. Yuyama K, Yanagisawa K. Late endocytic dysfunction as a putative cause of amyloid fibril formation in Alzheimer's disease. J Neurochem. 2009;109:1250-60 pubmed publisher
    ..Our results suggest that late but not early endocytic dysfunction contributes to the amyloid fibril formation by facilitating the generation of amyloid seed in the Alzheimer's brain. ..
  26. Salinas S, Zussy C, Loustalot F, Henaff D, Menendez G, Morton P, et al. Disruption of the coxsackievirus and adenovirus receptor-homodimeric interaction triggers lipid microdomain- and dynamin-dependent endocytosis and lysosomal targeting. J Biol Chem. 2014;289:680-95 pubmed publisher
    ..Moreover, ligands that disrupted the homodimeric CAR interactions in its D1 domains triggered an internalization cascade involving sequences in its intracellular tail. ..
  27. Coradeghini R, Gioria S, Garcia C, Nativo P, Franchini F, Gilliland D, et al. Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. Toxicol Lett. 2013;217:205-16 pubmed publisher
    ..No significant effect was observed in the expression level of caveolin, while reduction of the expression and degradation of the clathrin heavy chain was observed in cells exposed for 72 h to AuNPs...
  28. Molinete M, Dupuis S, Brodsky F, Halban P. Role of clathrin in the regulated secretory pathway of pancreatic beta-cells. J Cell Sci. 2001;114:3059-66 pubmed
    ..These results confirm a role for clathrin in the removal of proteases from maturing granules, thus explaining the increased truncation and degradation of C-peptide in cells expressing Hub. ..
  29. Wang J, Virta V, Riddelle Spencer K, O Halloran T. Compromise of clathrin function and membrane association by clathrin light chain deletion. Traffic. 2003;4:891-901 pubmed
    While clathrin heavy chains from different species are highly conserved in amino acid sequence, clathrin light chains are much more divergent. Thus clathrin light chain may have different functions in different organisms...
  30. Musch M, Arvans D, Walsh Reitz M, Uchiyama K, Fukuda M, Chang E. Synaptotagmin I binds intestinal epithelial NHE3 and mediates cAMP- and Ca2+-induced endocytosis by recruitment of AP2 and clathrin. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1549-58 pubmed
  31. Escobar G, McIntyre R, Moore E, Gamboni Robertson F, Banerjee A. Clathrin heavy chain is required for TNF-induced inflammatory signaling. Surgery. 2006;140:268-72 pubmed
    ..CHCsil significantly impairs phosphorylation of both I kappaB alpha and P65. CHCsil also significantly decreased MCP-1 production. These data suggest that CHC is required for certain TNF-alpha-induced, inflammatory signaling pathways. ..
  32. Morón J, Abul Husn N, Rozenfeld R, Dolios G, Wang R, Devi L. Morphine administration alters the profile of hippocampal postsynaptic density-associated proteins: a proteomics study focusing on endocytic proteins. Mol Cell Proteomics. 2007;6:29-42 pubmed
    ..Taken together, these results suggest that, by causing a redistribution of endocytic proteins at the synapse, morphine modulates synaptic plasticity at hippocampal glutamatergic synapses. ..
  33. Chen C, Ingram M, Rosal P, Graham T. Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J Cell Biol. 1999;147:1223-36 pubmed
    ..These observations indicate a novel role for a P-type ATPase in late Golgi function and suggest a possible link between membrane asymmetry and clathrin function at the Golgi complex. ..
  34. Wang C, Yan X, Chen Q, Jiang N, Fu W, Ma B, et al. Clathrin light chains regulate clathrin-mediated trafficking, auxin signaling, and development in Arabidopsis. Plant Cell. 2013;25:499-516 pubmed publisher
    ..These results suggest that CLCs are key regulators in clathrin-mediated trafficking downstream of ABP1-mediated signaling and thus play a critical role in membrane trafficking from the TGN/EE and PM during plant development. ..
  35. Chen D, Jian Y, Liu X, Zhang Y, Liang J, Qi X, et al. Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans. PLoS Genet. 2013;9:e1003517 pubmed publisher
    ..These findings reveal a non-classical role of clathrin and AP2 and establish them as indispensable regulators in phagocytic receptor-mediated apoptotic cell clearance...
  36. Lauvrak S, Torgersen M, Sandvig K. Efficient endosome-to-Golgi transport of Shiga toxin is dependent on dynamin and clathrin. J Cell Sci. 2004;117:2321-31 pubmed
  37. Ma M, Robinson P, Chircop M. Sorting nexin 9 recruits clathrin heavy chain to the mitotic spindle for chromosome alignment and segregation. PLoS ONE. 2013;8:e68387 pubmed publisher
    ..Therefore SNX9 and CHC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association. ..
  38. Satoh M, Akatsu T, Ishkawa Y, Minami Y, Nakamura M. A novel activator of C-C chemokine, FROUNT, is expressed with C-C chemokine receptor 2 and its ligand in failing human heart. J Card Fail. 2007;13:114-9 pubmed
    ..The expression of FOUNT-mediated CCL2/CCR2 may have important implications in the pathogenesis of CHF. The CCL2/CCR2 pathway via FROUNT may influence the clinical severity of CHF. ..
  39. Brandenburg B, Lee L, Lakadamyali M, Rust M, Zhuang X, Hogle J. Imaging poliovirus entry in live cells. PLoS Biol. 2007;5:e183 pubmed
    ..We expect this imaging assay to be broadly applicable to the investigation of entry mechanisms for nonenveloped viruses. ..
  40. Walchli S, Aasheim H, Skånland S, Spilsberg B, Torgersen M, Rosendal K, et al. Characterization of clathrin and Syk interaction upon Shiga toxin binding. Cell Signal. 2009;21:1161-8 pubmed publisher
    ..We show that these phosphorylated residues act as binding sites for the direct interaction between Syk and CHC. Interestingly, Syk-CHC complex formation could be induced by both Stx and B cell receptor stimulation. ..
  41. Endo Y, Sugiyama A, Li S, Ohmori K, Ohata H, Yoshida Y, et al. Regulation of clathrin-mediated endocytosis by p53. Genes Cells. 2008;13:375-86 pubmed publisher
    ..Thus, our findings provide evidence that cytosolic p53 may participate in the regulation of clathrin-mediated endocytosis to control the correct signaling from EGFR. ..
  42. Peralta S, Gómez Y, González Gaitán M, Moya F, Vinós J. Notch down-regulation by endocytosis is essential for pigment cell determination and survival in the Drosophila retina. Mech Dev. 2009;126:256-69 pubmed publisher
    ..We discuss the implications of these findings for current models on eye-development and for the role of endocytosis in Notch signaling. ..
  43. Perry D, Daugherty G, Martin W. Clathrin-coated pit-associated proteins are required for alveolar macrophage phagocytosis. J Immunol. 1999;162:380-6 pubmed
    ..01). Ab blockade of hsc70, which catalyzes clathrin turnover, also inhibited phagocytosis from 9.1+/-0.5 to 4.3+/-0.2 (p<0.01). These findings suggest that clathrin-mediated receptor/membrane recycling is required for phagocytosis. ..
  44. Wang Q, Zhao Y, Luo W, Li R, He Q, Fang X, et al. Single-particle analysis reveals shutoff control of the Arabidopsis ammonium transporter AMT1;3 by clustering and internalization. Proc Natl Acad Sci U S A. 2013;110:13204-9 pubmed publisher
    ..Our results revealed that the clustering and endocytosis of AMT1;3 provides an effective mechanism by which plant cells can avoid accumulation of toxic levels of ammonium by eliminating active AMT1;3 from the plasma membrane. ..
  45. Gall W, Geething N, Hua Z, Ingram M, Liu K, Chen S, et al. Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. Curr Biol. 2002;12:1623-7 pubmed
    ..These data provide the first in vivo evidence for an integral membrane protein requirement in forming CCVs. ..
  46. Kitahara H, Masumoto J, Parker A, Maruta F, Kubo N, Shimizu A, et al. COP35, a cholangiocarcinoma-binding oligopeptide, interacts with the clathrin heavy chain accompanied by GRP78. Mol Cancer Res. 2011;9:688-701 pubmed publisher
    ..Utilizing pull-down assay and liquid chromatography, we identify the clathrin heavy chain accompanied by GRP78/BiP as a COP35-binding partner. In summary, we identify COP35 as a possible candidate for peptide-targeted therapies for CCA...
  47. Shen H, Ferguson S, Dephoure N, Park R, Yang Y, Volpicelli Daley L, et al. Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin. Mol Biol Cell. 2011;22:493-502 pubmed publisher
    ..These findings reveal a link between progression of clathrin-coated pits to endocytic vesicles and an activation-deactivation cycle of Ack. ..
  48. Mohrlüder J, Hoffmann Y, Stangler T, Hänel K, Willbold D. Identification of clathrin heavy chain as a direct interaction partner for the gamma-aminobutyric acid type A receptor associated protein. Biochemistry. 2007;46:14537-43 pubmed
  49. Ihara Y, Yasuoka C, Kageyama K, Wada Y, Kondo T. Tyrosine phosphorylation of clathrin heavy chain under oxidative stress. Biochem Biophys Res Commun. 2002;297:353-60 pubmed
    ..The present study demonstrates that oxidative stress affects intracellular vesicular trafficking via the alteration of clathrin-dependent vesicular trafficking. ..
  50. Alhoot M, Wang S, Sekaran S. Inhibition of dengue virus entry and multiplication into monocytes using RNA interference. PLoS Negl Trop Dis. 2011;5:e1410 pubmed publisher
    ..This might serve as a novel promising therapeutic target to attenuate dengue infection and thus reduce transmission as well as progression to severe dengue hemorrhagic fever. ..
  51. Natesan S, Black A, Matthews K, Mottram J, Field M. Trypanosoma brucei brucei: endocytic recycling is important for mouse infectivity. Exp Parasitol. 2011;127:777-83 pubmed publisher
    ..These data indicate that trypanosomes likely tolerate the effects of partly decreased clathrin expression and alterations in early endocytosis, but are more sensitive to alterations in the recycling arm of the pathway. ..
  52. Denny P, Morgan G, Field M, Smith D. Leishmania major: clathrin and adaptin complexes of an intra-cellular parasite. Exp Parasitol. 2005;109:33-7 pubmed
    ..Clathrin relocalises in amastigotes relative to promastigotes, consistent with developmental alterations to the morphology of the endo-membrane system. ..
  53. Collin G, Franco M, Simon V, Benistant C, Roche S. The Tom1L1-clathrin heavy chain complex regulates membrane partitioning of the tyrosine kinase Src required for mitogenic and transforming activities. Mol Cell Biol. 2007;27:7631-40 pubmed
    ..We concluded that the Tom1L1-CHC complex defines a novel mechanism involved in negative regulation of mitogenic and transforming signals, by modulating SFK partitioning at the plasma membrane. ..