monomeric clathrin assembly proteins


Summary: A subclass of clathrin assembly proteins that occur as monomers.

Top Publications

  1. Zhao X, Greener T, Al Hasani H, Cushman S, Eisenberg E, Greene L. Expression of auxilin or AP180 inhibits endocytosis by mislocalizing clathrin: evidence for formation of nascent pits containing AP1 or AP2 but not clathrin. J Cell Sci. 2001;114:353-65 pubmed
  2. Morgan J, Prasad K, Hao W, Augustine G, Lafer E. A conserved clathrin assembly motif essential for synaptic vesicle endocytosis. J Neurosci. 2000;20:8667-76 pubmed
    ..These results reveal the structural basis for clathrin assembly and provide novel insights into the molecular mechanism of clathrin-mediated synaptic vesicle endocytosis. ..
  3. Dreyling M, Martinez Climent J, Zheng M, Mao J, Rowley J, Bohlander S. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family. Proc Natl Acad Sci U S A. 1996;93:4804-9 pubmed
    ..The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. ..
  4. Morgan J, Zhao X, Womack M, Prasad K, Augustine G, Lafer E. A role for the clathrin assembly domain of AP180 in synaptic vesicle endocytosis. J Neurosci. 1999;19:10201-12 pubmed
  5. Yao P, Coleman P, Calkins D. High-resolution localization of clathrin assembly protein AP180 in the presynaptic terminals of mammalian neurons. J Comp Neurol. 2002;447:152-62 pubmed
  6. Nonet M, Holgado A, Brewer F, Serpe C, Norbeck B, Holleran J, et al. UNC-11, a Caenorhabditis elegans AP180 homologue, regulates the size and protein composition of synaptic vesicles. Mol Biol Cell. 1999;10:2343-60 pubmed
    ..We propose that the UNC-11 protein mediates two functions during synaptic vesicle biogenesis: it recruits synaptobrevin to synaptic vesicle membranes and it regulates the size of the budded vesicle during clathrin coat assembly. ..
  7. Zhen L, Jiang S, Feng L, Bright N, Peden A, Seymour A, et al. Abnormal expression and subcellular distribution of subunit proteins of the AP-3 adaptor complex lead to platelet storage pool deficiency in the pearl mouse. Blood. 1999;94:146-55 pubmed
    ..These and related experiments strongly suggest that the AP-3 complex regulates the biogenesis/function of organelles of platelets and other cells and that abrogation of expression of the AP-3 complex leads to platelet SPD. ..
  8. Honing S, Sandoval I, Von Figura K. A di-leucine-based motif in the cytoplasmic tail of LIMP-II and tyrosinase mediates selective binding of AP-3. EMBO J. 1998;17:1304-14 pubmed
    ..This points to a function of AP-3 in intracellular sorting to lysosomes and melanosomes of a subset of cargo proteins via di-leucine-based sorting motifs. ..
  9. Corneveaux J, Myers A, Allen A, Pruzin J, Ramirez M, Engel A, et al. Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals. Hum Mol Genet. 2010;19:3295-301 pubmed publisher

More Information


  1. Dell Angelica E, Ohno H, Ooi C, Rabinovich E, Roche K, Bonifacino J. AP-3: an adaptor-like protein complex with ubiquitous expression. EMBO J. 1997;16:917-28 pubmed
    ..These results suggest that the sigma3 chains are components of a novel, ubiquitous adaptor-like complex involved in the recognition of tyrosine-based sorting signals. ..
  2. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere M, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 2009;41:1088-93 pubmed publisher
    ..5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86). ..
  3. Mettlen M, Stoeber M, Loerke D, Antonescu C, Danuser G, Schmid S. Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits. Mol Biol Cell. 2009;20:3251-60 pubmed publisher
  4. Deshpande A, Cusan M, Rawat V, Reuter H, Krause A, Pott C, et al. Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia. Cancer Cell. 2006;10:363-74 pubmed
    ..These data demonstrate in a murine leukemia model that AML can be propagated by a transformed progenitor with lymphoid characteristics, which can be targeted by antibodies that do not crossreact with normal HSCs. ..
  5. Hussain N, Yamabhai M, Bhakar A, Metzler M, Ferguson S, Hayden M, et al. A role for epsin N-terminal homology/AP180 N-terminal homology (ENTH/ANTH) domains in tubulin binding. J Biol Chem. 2003;278:28823-30 pubmed
    ..These data demonstrate an evolutionarily conserved property of ENTH domains to interact with tubulin and microtubules. ..
  6. Simpson F, Peden A, Christopoulou L, Robinson M. Characterization of the adaptor-related protein complex, AP-3. J Cell Biol. 1997;137:835-45 pubmed
  7. Greener T, Zhao X, Nojima H, Eisenberg E, Greene L. Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. J Biol Chem. 2000;275:1365-70 pubmed
    ..We propose that GAK is a required cofactor for the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. ..
  8. Ford M, Pearse B, Higgins M, Vallis Y, Owen D, Gibson A, et al. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science. 2001;291:1051-5 pubmed
    ..This was shown by using purified components and a budding assay on preformed lipid monolayers. In the presence of AP180, clathrin lattices formed on the monolayer. When AP2 was also present, coated pits were formed...
  9. Newpher T, Smith R, Lemmon V, Lemmon S. In vivo dynamics of clathrin and its adaptor-dependent recruitment to the actin-based endocytic machinery in yeast. Dev Cell. 2005;9:87-98 pubmed
    ..In contrast, Sla2p, End3p, Pan1p, and a dynamic actin cytoskeleton are not required for clathrin assembly or exchange but are required for the mobility, maturation, and/or turnover of clathrin-containing endocytic structures. ..
  10. Barth M, Holstein S. Identification and functional characterization of Arabidopsis AP180, a binding partner of plant alphaC-adaptin. J Cell Sci. 2004;117:2051-62 pubmed
    ..Deletion of the single DLL motif abolished the assembly activity of At-AP180 almost completely, but did not affect its binding to triskelia, suggesting the existence of additional binding determinants. ..
  11. Lambert J, Zelenika D, Hiltunen M, Chouraki V, Combarros O, Bullido M, et al. Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations. Neurobiol Aging. 2011;32:756.e11-5 pubmed publisher
    ..0 × 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. ..
  12. Suzuki M, Tanaka H, Tanimura A, Tanabe K, Oe N, Rai S, et al. The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice. PLoS ONE. 2012;7:e31854 pubmed publisher
    ..CALM-deficient erythroid cells and embryonic fibroblasts exhibited impaired clathrin-mediated endocytosis of transferrin. These results indicate that CALM is required for erythroid maturation and transferrin internalization in mice. ..
  13. Han S, Lee J, Hong S, Park S, Kim C, Song M, et al. AP180 binds to the C-terminal SH2 domain of phospholipase C-gamma1 and inhibits its enzymatic activity. Biochem Biophys Res Commun. 2002;290:35-41 pubmed
  14. Klebig M, Wall M, Potter M, Rowe E, Carpenter D, Rinchik E. Mutations in the clathrin-assembly gene Picalm are responsible for the hematopoietic and iron metabolism abnormalities in fit1 mice. Proc Natl Acad Sci U S A. 2003;100:8360-5 pubmed
    ..These mutants thus provide unique models for exploring how the endocytic function of mouse Picalm and the transport processes mediated by clathrin and the AP2 complex contribute to normal hematopoiesis, iron metabolism, and growth. ..
  15. Huang K, D hondt K, Riezman H, Lemmon S. Clathrin functions in the absence of heterotetrameric adaptors and AP180-related proteins in yeast. EMBO J. 1999;18:3897-908 pubmed
    ..Therefore, alternative mechanisms for clathrin assembly and coated vesicle formation, as well as the role of AP complexes and AP180-related proteins in these processes, must be considered. ..
  16. Maritzen T, Koo S, Haucke V. Turning CALM into excitement: AP180 and CALM in endocytosis and disease. Biol Cell. 2012;104:588-602 pubmed publisher
  17. Panek H, Stepp J, Engle H, Marks K, Tan P, Lemmon S, et al. Suppressors of YCK-encoded yeast casein kinase 1 deficiency define the four subunits of a novel clathrin AP-like complex. EMBO J. 1997;16:4194-204 pubmed
    ..These results suggest that vesicle trafficking at the plasma membrane requires the activity of Yck protein kinases, and that the new AP-related complex may participate in this process. ..
  18. Deshpande A, Rouhi A, Lin Y, Stadler C, Greif P, Arseni N, et al. The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice. Leukemia. 2011;25:1718-27 pubmed publisher
    ..These findings further suggest that future approaches to antagonize CALM-AF10-induced transformation should incorporate strategies, which aim at blocking these key domains. ..
  19. Ooi C, Moreira J, Dell Angelica E, Poy G, Wassarman D, Bonifacino J. Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila eye color mutant garnet. EMBO J. 1997;16:4508-18 pubmed
    ..Thus, the eye pigmentation defect in the Drosophila garnet mutant may be attributed to compromised function of a coat protein involved in intracellular transport processes required for biogenesis or function of pigment granules. ..
  20. Archangelo L, Glasner J, Krause A, Bohlander S. The novel CALM interactor CATS influences the subcellular localization of the leukemogenic fusion protein CALM/AF10. Oncogene. 2006;25:4099-109 pubmed
    ..Expression of CATS was able to markedly increase the nuclear localization of CALM and of the leukemogenic fusion protein CALM/AF10. The possible implications of these findings for CALM/AF10-mediated leukemogenesis are discussed. ..
  21. Baig S, Joseph S, Tayler H, Abraham R, Owen M, Williams J, et al. Distribution and expression of picalm in Alzheimer disease. J Neuropathol Exp Neurol. 2010;69:1071-7 pubmed publisher
    ..Further research is needed to determine whether PICALM expression is influenced by A? levels and whether it affects A? uptake and transport by endothelial cells. ..
  22. Carrasquillo M, Belbin O, Hunter T, Ma L, Bisceglio G, Zou F, et al. Replication of CLU, CR1, and PICALM associations with alzheimer disease. Arch Neurol. 2010;67:961-4 pubmed publisher
    ..These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD. ..
  23. Jones L, Harold D, Williams J. Genetic evidence for the involvement of lipid metabolism in Alzheimer's disease. Biochim Biophys Acta. 2010;1801:754-61 pubmed publisher
    ..Four new genes for common AD have been revealed in the past year, CLU, CR1, PICALM and BIN1. Their possible involvement in lipid metabolism and how that relates to AD is discussed here. ..
  24. Faundez V, Horng J, Kelly R. A function for the AP3 coat complex in synaptic vesicle formation from endosomes. Cell. 1998;93:423-32 pubmed
    ..Budding from washed membranes can be reconstituted with purified AP3 and recombinant ARF1. We conclude that AP3 coating is involved in at least one pathway of small vesicle formation from endosomes. ..
  25. Hom R, Vora M, Regner M, Subach O, Cho W, Verkhusha V, et al. pH-dependent binding of the Epsin ENTH domain and the AP180 ANTH domain to PI(4,5)P2-containing bilayers. J Mol Biol. 2007;373:412-23 pubmed
    ..The pH sensitivity of the ENTH and ANTH domains is reminiscent to the pH dependency of the FYVE domain suggesting a common regulatory mechanism of membrane anchoring by a subset of the PI-binding domains. ..
  26. Silliman C, McGavran L, Wei Q, Miller L, Li S, Hunger S. Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-14;q14-q21) suggests a potential role for truncated AF10 polypeptides. Leukemia. 1998;12:1404-10 pubmed
  27. Legendre Guillemin V, Wasiak S, Hussain N, Angers A, McPherson P. ENTH/ANTH proteins and clathrin-mediated membrane budding. J Cell Sci. 2004;117:9-18 pubmed
  28. Yao P, Zhang P, Mattson M, Furukawa K. Heterogeneity of endocytic proteins: distribution of clathrin adaptor proteins in neurons and glia. Neuroscience. 2003;121:25-37 pubmed
    ..The findings also provide information on the distribution of AP2, CALM, and epsin 1 in cells of the nervous system that suggest different roles for these endocytic proteins in the biology of these cells. ..
  29. Cho J, Oh D, Kim H, Park S, Choi H, Kwon S, et al. The TSP motif in AP180 inhibits phospholipase D1 activity resulting in increased efficacy of anticancer drug via its direct binding to carboxyl terminal of phospholipase D1. Cancer Lett. 2011;302:144-54 pubmed publisher
    ..These results indicated that Thr312-Pro314 (especially Ser313 as a phosphorylation residue) of hAP180 can regulate hPLD1 activity through binding with the C-terminal region of PLD1. ..
  30. Hao W, Luo Z, Zheng L, Prasad K, Lafer E. AP180 and AP-2 interact directly in a complex that cooperatively assembles clathrin. J Biol Chem. 1999;274:22785-94 pubmed
    ..Phosphorylation of AP180, by modulating the affinity of AP180 for AP-2, may contribute to the regulation of clathrin assembly in vivo. ..
  31. Wen Y, Stavrou I, Bersuker K, Brady R, De Lozanne A, O Halloran T. AP180-mediated trafficking of Vamp7B limits homotypic fusion of Dictyostelium contractile vacuoles. Mol Biol Cell. 2009;20:4278-88 pubmed publisher
    ..Dictyostelium contractile vacuoles offer a valuable system to study clathrin-coated vesicles on internal organelles within eukaryotic cells. ..
  32. Morris S, Schroder S, Plessmann U, Weber K, Ungewickell E. Clathrin assembly protein AP180: primary structure, domain organization and identification of a clathrin binding site. EMBO J. 1993;12:667-75 pubmed
    ..AP180 shows no significant homology to known clathrin binding proteins, but is nearly identical to a mouse phosphoprotein (F1-20). This protein, localized to synaptic termini, has so far been of unknown function. ..
  33. Drake M, Zhu Y, Kornfeld S. The assembly of AP-3 adaptor complex-containing clathrin-coated vesicles on synthetic liposomes. Mol Biol Cell. 2000;11:3723-36 pubmed
    ..These results establish that AP-3-containing clathrin-coated vesicles form in vitro and are consistent with AP-3-dependent protein transport being mediated by clathrin-coated vesicles...
  34. Vecchi M, Polo S, Poupon V, Van de Loo J, Benmerah A, Di Fiore P. Nucleocytoplasmic shuttling of endocytic proteins. J Cell Biol. 2001;153:1511-7 pubmed
  35. Feng L, Seymour A, Jiang S, To A, Peden A, Novak E, et al. The beta3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and night blindness. Hum Mol Genet. 1999;8:323-30 pubmed
    ..These experiments also suggest mutations in AP-3 subunits as a basis for unique forms of human Hermansky-Pudlak syndrome and congenital night blindness, for which the pearl mouse is an appropriate animal model. ..
  36. Koo S, Markovic S, Puchkov D, Mahrenholz C, Beceren Braun F, Maritzen T, et al. SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses. Proc Natl Acad Sci U S A. 2011;108:13540-5 pubmed publisher
    ..Defective SNARE endocytosis may also underlie the association of CALM and AP180 with neurodevelopmental and cognitive defects or neurodegenerative disorders...
  37. Harel A, Wu F, Mattson M, Morris C, Yao P. Evidence for CALM in directing VAMP2 trafficking. Traffic. 2008;9:417-29 pubmed publisher
    ..Thus, our results reveal a role for CALM in directing VAMP2 trafficking during endocytosis. ..
  38. Burston H, Maldonado Baez L, Davey M, Montpetit B, Schluter C, Wendland B, et al. Regulators of yeast endocytosis identified by systematic quantitative analysis. J Cell Biol. 2009;185:1097-110 pubmed publisher
    ..Our findings highlight the conserved machinery and reveal novel mechanisms that underlie endocytic internalization. ..
  39. Jun G, Naj A, Beecham G, Wang L, Buros J, Gallins P, et al. Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch Neurol. 2010;67:1473-84 pubmed publisher
    ..Genotypes at PICALM confer risk predominantly in APOE ε4-positive subjects. Thus, APOE and PICALM synergistically interact. ..
  40. Dell Angelica E, Klumperman J, Stoorvogel W, Bonifacino J. Association of the AP-3 adaptor complex with clathrin. Science. 1998;280:431-4 pubmed
    ..AP-3 colocalized with clathrin in cells as observed by immunofluorescence and immunoelectron microscopy. Thus, AP-3 function in protein sorting may depend on clathrin. ..
  41. Treusch S, Hamamichi S, Goodman J, Matlack K, Chung C, Baru V, et al. Functional links between A? toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast. Science. 2011;334:1241-5 pubmed publisher
    ..Thus, links between A?, endocytosis, and human AD risk factors can be ascertained with yeast as a model system. ..
  42. Cowles C, Odorizzi G, Payne G, Emr S. The AP-3 adaptor complex is essential for cargo-selective transport to the yeast vacuole. Cell. 1997;91:109-18 pubmed
    ..This study, therefore, provides evidence that the AP-3 complex functions in cargo-selective protein transport from the Golgi to the vacuole/lysosome. ..
  43. Yao P, Petralia R, Bushlin I, Wang Y, Furukawa K. Synaptic distribution of the endocytic accessory proteins AP180 and CALM. J Comp Neurol. 2005;481:58-69 pubmed
    ..We propose that both AP180 and CALM function as endocytic accessory proteins at synapses, but each may regulate distinct clathrin pathways. ..
  44. Bushlin I, Petralia R, Wu F, Harel A, Mughal M, Mattson M, et al. Clathrin assembly protein AP180 and CALM differentially control axogenesis and dendrite outgrowth in embryonic hippocampal neurons. J Neurosci. 2008;28:10257-71 pubmed publisher
    ..Additionally, CALM-deficient neurons show disrupted secretory transport. Our data demonstrate previously unknown functions for AP180 and CALM in intracellular trafficking that are essential in the growth of neurons. ..
  45. Cousin M, Tan T, Robinson P. Protein phosphorylation is required for endocytosis in nerve terminals: potential role for the dephosphins dynamin I and synaptojanin, but not AP180 or amphiphysin. J Neurochem. 2001;76:105-16 pubmed
    ..Therefore, phosphorylation of a subset of dephosphins, which includes dynamin I and synaptojanin, is required for the next round of stimulated synaptic vesicle retrieval. ..
  46. Meyerholz A, Hinrichsen L, Groos S, Esk P, Brandes G, Ungewickell E. Effect of clathrin assembly lymphoid myeloid leukemia protein depletion on clathrin coat formation. Traffic. 2005;6:1225-34 pubmed
    ..Taken together, our findings indicate a critical role for CALM in the regulation and orderly progression of coated bud formation at the plasma membrane. ..
  47. Zhang B, Koh Y, Beckstead R, Budnik V, Ganetzky B, Bellen H. Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis. Neuron. 1998;21:1465-75 pubmed
    ..These results provide novel insights into the molecular mechanism of endocytosis and reveal a role for AP180 in regulating vesicle size through a clathrin-dependent reassembly process. ..
  48. Wechsler D, Engstrom L, Alexander B, Motto D, Roulston D. A novel chromosomal inversion at 11q23 in infant acute myeloid leukemia fuses MLL to CALM, a gene that encodes a clathrin assembly protein. Genes Chromosomes Cancer. 2003;36:26-36 pubmed
  49. Tebar F, Bohlander S, Sorkin A. Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic. Mol Biol Cell. 1999;10:2687-702 pubmed
    ..Altogether, the data suggest that CALM is an important component of coated pit internalization machinery, possibly involved in the regulation of clathrin recruitment to the membrane and/or the formation of the coated pit. ..
  50. Kalthoff C, Alves J, Urbanke C, Knorr R, Ungewickell E. Unusual structural organization of the endocytic proteins AP180 and epsin 1. J Biol Chem. 2002;277:8209-16 pubmed
  51. Dittman J, Kaplan J. Factors regulating the abundance and localization of synaptobrevin in the plasma membrane. Proc Natl Acad Sci U S A. 2006;103:11399-404 pubmed
    ..The size of the reservoir is set by the relative rates of exo- and endocytosis. ..
  52. Miller S, Sahlender D, Graham S, Höning S, Robinson M, Peden A, et al. The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM. Cell. 2011;147:1118-31 pubmed publisher
    ..CALM's role in directing the endocytosis of small R-SNAREs may provide insight into the association of CALM/PICALM mutations with growth retardation, cognitive defects, and Alzheimer's disease. ..
  53. Bao H, Daniels R, MacLeod G, Charlton M, Atwood H, Zhang B. AP180 maintains the distribution of synaptic and vesicle proteins in the nerve terminal and indirectly regulates the efficacy of Ca2+-triggered exocytosis. J Neurophysiol. 2005;94:1888-903 pubmed
    ..These results suggest that AP180 is required for either recycling vesicle proteins and/or maintaining the distribution of both vesicle and synaptic proteins in the nerve terminal. ..