adaptor protein complex mu subunits


Summary: A family of medium adaptin protein subunits of approximately 45 KDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 3 and ADAPTOR PROTEIN COMPLEX 4.

Top Publications

  1. Owen D, Evans P. A structural explanation for the recognition of tyrosine-based endocytotic signals. Science. 1998;282:1327-32 pubmed
    ..Specificity was conferred by hydrophobic pockets that bind the tyrosine and leucine in the peptide. In the crystal, the protein forms dimers that could increase the strength and specificity of binding to dimeric receptors. ..
  2. Aguilar R, Ohno H, Roche K, Bonifacino J. Functional domain mapping of the clathrin-associated adaptor medium chains mu1 and mu2. J Biol Chem. 1997;272:27160-6 pubmed
  3. de Chassey B, Dubois A, Lefkir Y, Letourneur F. Identification of clathrin-adaptor medium chains in Dictyostelium discoideum: differential expression during development. Gene. 2001;262:115-22 pubmed
    ..discoideum and strengthens this attractive model organism for studying the function of coat complexes in vivo. ..
  4. Kita A, Sugiura R, Shoji H, He Y, Deng L, Lu Y, et al. Loss of Apm1, the micro1 subunit of the clathrin-associated adaptor-protein-1 complex, causes distinct phenotypes and synthetic lethality with calcineurin deletion in fission yeast. Mol Biol Cell. 2004;15:2920-31 pubmed
  5. Meyer C, Zizioli D, Lausmann S, Eskelinen E, Hamann J, Saftig P, et al. mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors. EMBO J. 2000;19:2193-203 pubmed
    ..MPR46 fails to recycle back from the endosome to the TGN, indicating that AP-1 is required for retrograde endosome to TGN transport of the receptor. ..
  6. Ma Y, Takeuchi M, Sugiura R, Sio S, Kuno T. Deletion mutants of AP-1 adaptin subunits display distinct phenotypes in fission yeast. Genes Cells. 2009;14:1015-28 pubmed publisher
    ..Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes. ..
  7. Pauloin A, Thurieau C. The 50 kDa protein subunit of assembly polypeptide (AP) AP-2 adaptor from clathrin-coated vesicles is phosphorylated on threonine-156 by AP-1 and a soluble AP50 kinase which co-purifies with the assembly polypeptides. Biochem J. 1993;296 ( Pt 2):409-15 pubmed
    ..This AP50 kinase activity corresponded to a 280 kDa protein complex according to gel-filtration data...
  8. Page L, Robinson M. Targeting signals and subunit interactions in coated vesicle adaptor complexes. J Cell Biol. 1995;131:619-30 pubmed
    ..These results indicate that the adaptor subunits act in concert to target the complex to the appropriate membrane. ..
  9. Collins B, McCoy A, Kent H, Evans P, Owen D. Molecular architecture and functional model of the endocytic AP2 complex. Cell. 2002;109:523-35 pubmed
    ..A model for AP2 recruitment and activation is proposed. ..

More Information


  1. Charette S, Mercanti V, Letourneur F, Bennett N, Cosson P. A role for adaptor protein-3 complex in the organization of the endocytic pathway in Dictyostelium. Traffic. 2006;7:1528-38 pubmed
    ..Our results suggest that AP-3 plays an essential role in the compartmentalization of the endocytic pathway in Dictyostelium. ..
  2. Matsui W, Kirchhausen T. Stabilization of clathrin coats by the core of the clathrin-associated protein complex AP-2. Biochemistry. 1990;29:10791-8 pubmed
    ..These results are consistent with the proposal that the AP core contains the binding site(s) for clathrin, while the alpha- and beta-chain appendages interact with membrane components of coated pits and coated vesicles...
  3. Eskelinen E, Meyer C, Ohno H, von Figura K, Schu P. The polarized epithelia-specific mu 1B-adaptin complements mu 1A-deficiency in fibroblasts. EMBO Rep. 2002;3:471-7 pubmed
    ..This demonstrates that mu 1A and mu 1B do have overlapping sorting functions and indicates that AP-1A and AP-1B mediate protein sorting along parallel pathways between the TGN and endosomes in polarized epithelia. ..
  4. FOLSCH H, Ohno H, Bonifacino J, Mellman I. A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell. 1999;99:189-98 pubmed
    ..We conclude that basolateral sorting is mediated by an epithelial cell-specific version of the AP-1 complex containing mu1B...
  5. Craig H, Reddy T, Riggs N, Dao P, Guatelli J. Interactions of HIV-1 nef with the mu subunits of adaptor protein complexes 1, 2, and 3: role of the dileucine-based sorting motif. Virology. 2000;271:9-17 pubmed
  6. FOLSCH H, Pypaert M, Maday S, Pelletier L, Mellman I. The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains. J Cell Biol. 2003;163:351-62 pubmed
    ..Thus, despite the similarity of the two AP-1 complexes, AP-1A and AP-1B exhibit great specificity for endosomal transport versus cell polarity...
  7. Coleman S, Van Damme N, Day J, Noviello C, Hitchin D, Madrid R, et al. Leucine-specific, functional interactions between human immunodeficiency virus type 1 Nef and adaptor protein complexes. J Virol. 2005;79:2066-78 pubmed
    ..This binding likely underlies the unusual ability of Nef to induce the stabilization of these complexes on endosomal membranes, an activity that correlates with enhancement of viral replication. ..
  8. Ling K, Bairstow S, Carbonara C, Turbin D, Huntsman D, Anderson R. Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin. J Cell Biol. 2007;176:343-53 pubmed
  9. Nesterov A, Carter R, Sorkina T, Gill G, Sorkin A. Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant mu2 subunit and its effects on endocytosis. EMBO J. 1999;18:2489-99 pubmed
  10. Olusanya O, Andrews P, Swedlow J, Smythe E. Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo. Curr Biol. 2001;11:896-900 pubmed
    ..Here, we show that phosphorylation of a single threonine residue (Thr156) of the mu2 subunit of the AP2 complex is essential for efficient endocytosis of transferrin both in an in vitro coated-pit budding assay and in living cells...
  11. Geyer M, Yu H, Mandic R, Linnemann T, Zheng Y, Fackler O, et al. Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machinery. J Biol Chem. 2002;277:28521-9 pubmed
    ..Finally, blocking the expression of V1H decreased the enhancement of virion infectivity by Nef. Thus, V1H can function as an adaptor for interactions between Nef and AP-2. ..
  12. Rohde G, Wenzel D, Haucke V. A phosphatidylinositol (4,5)-bisphosphate binding site within mu2-adaptin regulates clathrin-mediated endocytosis. J Cell Biol. 2002;158:209-14 pubmed
    ..We suggest that PI(4,5)P2 binding to mu2-adaptin regulates clathrin-mediated endocytosis and thereby may contribute to structurally linking cargo recognition to coat formation. ..
  13. FOLSCH H, Pypaert M, Schu P, Mellman I. Distribution and function of AP-1 clathrin adaptor complexes in polarized epithelial cells. J Cell Biol. 2001;152:595-606 pubmed
  14. Roeth J, Williams M, Kasper M, Filzen T, Collins K. HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. J Cell Biol. 2004;167:903-13 pubmed
    ..In sum, our evidence suggests that binding of AP-1 to the Nef-MHC-I complex is an important step required for inhibition of antigen presentation by HIV. ..
  15. Ohno H, Tomemori T, Nakatsu F, Okazaki Y, Aguilar R, Foelsch H, et al. Mu1B, a novel adaptor medium chain expressed in polarized epithelial cells. FEBS Lett. 1999;449:215-20 pubmed
    ..Yeast two-hybrid analyses show that mu1B is capable of interacting with generic tyrosine-based sorting signals. These observations suggest that mu1B may be involved in protein sorting events specific to polarized cells. ..
  16. Krauss M, Kukhtina V, Pechstein A, Haucke V. Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes. Proc Natl Acad Sci U S A. 2006;103:11934-9 pubmed
    ..These data thus identify a positive feedback loop consisting of endocytic cargo proteins, AP-2mu, and PIPK type I which may provide a specific pool of PI(4,5)P(2) dedicated to clathrin/AP-2-dependent receptor internalization. ..
  17. Fu L, Rab A, Tang L, Rowe S, Bebok Z, Collawn J. Dab2 is a key regulator of endocytosis and post-endocytic trafficking of the cystic fibrosis transmembrane conductance regulator. Biochem J. 2012;441:633-43 pubmed publisher
    ..The results of the present study define a significant role for Dab2 both in the endocytosis and post-endocytic fate of CFTR. ..
  18. John B, Herrin B, Raman C, Wang Y, Bobbitt K, Brody B, et al. The B cell coreceptor CD22 associates with AP50, a clathrin-coated pit adapter protein, via tyrosine-dependent interaction. J Immunol. 2003;170:3534-43 pubmed
    ..In conclusion, these studies demonstrate that internalization of CD22 is dependent on its association with the AP-2 complex via tyrosine-based internalization motifs. ..
  19. Diril M, Wienisch M, Jung N, Klingauf J, Haucke V. Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling. Dev Cell. 2006;10:233-44 pubmed
    ..Our data identify stonin 2 as an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling. ..
  20. 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. ..
  21. Farías G, Cuitino L, Guo X, Ren X, Jarnik M, Mattera R, et al. Signal-mediated, AP-1/clathrin-dependent sorting of transmembrane receptors to the somatodendritic domain of hippocampal neurons. Neuron. 2012;75:810-23 pubmed publisher
    ..These findings highlight the primary recognition event that underlies somatodendritic sorting and contribute to the evolving view of AP-1 as a global regulator of cell polarity. ..
  22. Vissel B, Krupp J, Heinemann S, Westbrook G. A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux. Nat Neurosci. 2001;4:587-96 pubmed
    ..Our results provide a mechanism by which synaptic NMDA receptors can be modulated in a use-dependent manner even when the postsynaptic membrane is not sufficiently depolarized to relieve channel block by magnesium ions. ..
  23. Pearse B, Smith C, Owen D. Clathrin coat construction in endocytosis. Curr Opin Struct Biol. 2000;10:220-8 pubmed
  24. Johnson D, Webb M, Wisner T, Brunetti C. Herpes simplex virus gE/gI sorts nascent virions to epithelial cell junctions, promoting virus spread. J Virol. 2001;75:821-33 pubmed
    ..Delivery of virus particles to cell junctions would be expected to enhance virus spread and enable viruses to avoid host immune defenses. ..
  25. Huang M, Okada M, Nakatsu F, Oguni H, Ito M, Morita K, et al. Mutation screening of AP3M2 in Japanese epilepsy patients. Brain Dev. 2007;29:462-7 pubmed
  26. Zhang Y, Allison J. Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein. Proc Natl Acad Sci U S A. 1997;94:9273-8 pubmed
    ..These results suggest that AP50 and the coated pit adaptor complex AP2 may play an important role in regulating the intracellular trafficking and function of CTLA-4. ..
  27. Stephens D, Crump C, Clarke A, Banting G. Serine 331 and tyrosine 333 are both involved in the interaction between the cytosolic domain of TGN38 and the mu2 subunit of the AP2 clathrin adaptor complex. J Biol Chem. 1997;272:14104-9 pubmed
    ..In contrast to previously published work, our data suggest that not only Tyr-333 but also its context is important in determining the specificity of binding of TGN38 to mu2. ..
  28. 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
  29. Thurieau C, Brosius J, Burne C, Jolles P, Keen J, Mattaliano R, et al. Molecular cloning and complete amino acid sequence of AP50, an assembly protein associated with clathrin-coated vesicles. DNA. 1988;7:663-9 pubmed
    ..Comparison with the partially sequenced bovine brain AP50 shows a primary structure that is highly conserved. AP50 does not have detectable sequence similarity with other known kinases or with other proteins of known sequence. ..
  30. Ortiz Zapater E, Soriano Ortega E, Marcote M, Ortiz Masia D, Aniento F. Trafficking of the human transferrin receptor in plant cells: effects of tyrphostin A23 and brefeldin A. Plant J. 2006;48:757-70 pubmed
    ..The specific inhibition of Tfn/hTfR internalization and recycling by tyrphostin A23 and BFA, respectively, thus provide valuable molecular tools to characterize RME and the recycling pathway in plant cells. ..
  31. Hase K, Nakatsu F, Ohmae M, Sugihara K, Shioda N, Takahashi D, et al. AP-1B-mediated protein sorting regulates polarity and proliferation of intestinal epithelial cells in mice. Gastroenterology. 2013;145:625-35 pubmed publisher
    ..Loss of AP-1B in the intestinal epithelia results in mislocalization of E-cadherin, activation of ?-catenin/Tcf4 complex, proliferation, and hyperplasia. ..
  32. Shim J, Sternberg P, Lee J. Distinct and redundant functions of mu1 medium chains of the AP-1 clathrin-associated protein complex in the nematode Caenorhabditis elegans. Mol Biol Cell. 2000;11:2743-56 pubmed
    ..Thus, apm-1 and unc-101 encode two highly related micro1 chains that share redundant and distinct functions within AP-1 clathrin-associated protein complexes of the same tissue. ..
  33. Kirchhausen T, Nathanson K, Matsui W, Vaisberg A, Chow E, Burne C, et al. Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2. Proc Natl Acad Sci U S A. 1989;86:2612-6 pubmed
    ..Their amino-terminal domains are relatively invariant whereas their carboxyl-terminal domains are variable in both sequence and length. We propose that the variable domains select receptors for inclusion in coated vesicles. ..
  34. Singh R, Lau D, Noviello C, Ghosh P, Guatelli J. An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the mu subunit of the AP-1 endosomal coat complex. PLoS ONE. 2009;4:e8364 pubmed publisher
    ..The data also reveal an unexpected role for a hydrophobic pocket in micro1 for interaction with MHC-I CD/Nef. ..
  35. Smith E, Lima W, Charette S, Cosson P. Effect of starvation on the endocytic pathway in Dictyostelium cells. Eukaryot Cell. 2010;9:387-92 pubmed publisher
    ..Studying the endocytic pathway in starved cells can provide a different perspective, allowing the primary (invariant) defects resulting from specific mutations to be distinguished from their secondary (conditional) consequences. ..
  36. Yamamoto H, Sato A, Kikuchi A. Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst-mediated trafficking. J Biochem. 2017;162:317-326 pubmed publisher
    ..Thus, the polarized secretion of Wnt1 is regulated by different mechanisms than other Wnts...
  37. Whitfield S, Burston H, Bean B, Raghuram N, Maldonado Báez L, Davey M, et al. The alternate AP-1 adaptor subunit Apm2 interacts with the Mil1 regulatory protein and confers differential cargo sorting. Mol Biol Cell. 2016;27:588-98 pubmed publisher
    ..Interactions with specific regulatory factors may provide a general mechanism to diversify the functional repertoire of clathrin adaptor complexes. ..
  38. Happel N, Honing S, Neuhaus J, Paris N, Robinson D, Holstein S. Arabidopsis mu A-adaptin interacts with the tyrosine motif of the vacuolar sorting receptor VSR-PS1. Plant J. 2004;37:678-93 pubmed
    ..The trans-Golgi localization of the mu A-adaptin strongly suggests its involvement in Golgi- to vacuole-trafficking events. ..
  39. Liu Q, Feng Y, Forgac M. Activity and in vitro reassembly of the coated vesicle (H+)-ATPase requires the 50-kDa subunit of the clathrin assembly complex AP-2. J Biol Chem. 1994;269:31592-7 pubmed
    ..These results indicate that the AP50 polypeptide is necessary for both activity and in vitro reassembly of the V-ATPase complex. ..
  40. Thompson A, Nessler R, Wisco D, Anderson E, Winckler B, Sheff D. Recycling endosomes of polarized epithelial cells actively sort apical and basolateral cargos into separate subdomains. Mol Biol Cell. 2007;18:2687-97 pubmed
    ..This suggests that subdomain and transport vesicle formation occur as separate sorting steps and that both processes may contribute to sorting fidelity. ..
  41. Fields I, King S, Shteyn E, Kang R, FOLSCH H. Phosphatidylinositol 3,4,5-trisphosphate localization in recycling endosomes is necessary for AP-1B-dependent sorting in polarized epithelial cells. Mol Biol Cell. 2010;21:95-105 pubmed publisher
    ..In conclusion, PI(3,4,5)P(3) formation in recycling endosomes is essential for AP-1B function. ..
  42. Rohan S, Tu J, Kao J, Mukherjee P, Campagne F, Zhou X, et al. Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes. Clin Cancer Res. 2006;12:6937-45 pubmed
    ..To compare gene expression profiles of chromophobe renal cell carcinoma (RCC) and benign oncocytoma, aiming at identifying differentially expressed genes...
  43. Wernick N, Haucke V, Simister N. Recognition of the tryptophan-based endocytosis signal in the neonatal Fc Receptor by the mu subunit of adaptor protein-2. J Biol Chem. 2005;280:7309-16 pubmed
    ..These observations reveal a functional similarity between the tryptophan-based endocytosis signal and the YXXPhi motif, and an unexpected versatility of mu2 function. ..
  44. Iijima S, Lee Y, Ode H, Arold S, Kimura N, Yokoyama M, et al. A noncanonical mu-1A-binding motif in the N terminus of HIV-1 Nef determines its ability to downregulate major histocompatibility complex class I in T lymphocytes. J Virol. 2012;86:3944-51 pubmed publisher
    ..Our findings will help understanding of how HIV-1 evades the antiviral immune response by selectively redirecting the cellular protein trafficking system. ..
  45. Aguet F, Antonescu C, Mettlen M, Schmid S, Danuser G. Advances in analysis of low signal-to-noise images link dynamin and AP2 to the functions of an endocytic checkpoint. Dev Cell. 2013;26:279-91 pubmed publisher
    ..We identify dynamin and the EAP-binding ?-adaptin appendage domain of the AP2 adaptor as switches in a regulated, multistep maturation process and provide direct evidence for a molecular checkpoint in CME. ..
  46. Guo X, Mattera R, Ren X, Chen Y, Retamal C, González A, et al. The adaptor protein-1 μ1B subunit expands the repertoire of basolateral sorting signal recognition in epithelial cells. Dev Cell. 2013;27:353-66 pubmed publisher
    ..We conclude that expression of distinct μ1 isoforms in epithelial cells expands the repertoire of signals recognized by AP-1 for sorting of a broader range of cargoes to the basolateral surface. ..
  47. Verkerk A, Schot R, Dumee B, Schellekens K, Swagemakers S, Bertoli Avella A, et al. Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. Am J Hum Genet. 2009;85:40-52 pubmed publisher
  48. Kastning K, Kukhtina V, Kittler J, Chen G, Pechstein A, Enders S, et al. Molecular determinants for the interaction between AMPA receptors and the clathrin adaptor complex AP-2. Proc Natl Acad Sci U S A. 2007;104:2991-6 pubmed
    ..These data suggest that common mechanisms regulate AP-2-dependent internalization of pre- and postsynaptic membrane proteins. ..
  49. Friocourt G, Chafey P, Billuart P, Koulakoff A, Vinet M, Schaar B, et al. Doublecortin interacts with mu subunits of clathrin adaptor complexes in the developing nervous system. Mol Cell Neurosci. 2001;18:307-19 pubmed
    ..Taken together these data indicate that a certain proportion of Doublecortin interacts with AP-1 and/or AP-2 in vivo and are consistent with a potential involvement of Doublecortin in protein sorting or vesicular trafficking. ..
  50. Ohka S, Ohno H, Tohyama K, Nomoto A. Basolateral sorting of human poliovirus receptor alpha involves an interaction with the mu1B subunit of the clathrin adaptor complex in polarized epithelial cells. Biochem Biophys Res Commun. 2001;287:941-8 pubmed
    ..Thus, basolateral sorting of hPVRalpha appears to involve the interaction with mu1B through a tyrosine motif existing in the cytoplasmic domain. ..
  51. Usami Y, Popov S, Gottlinger H. The Nef-like effect of murine leukemia virus glycosylated gag on HIV-1 infectivity is mediated by its cytoplasmic domain and depends on the AP-2 adaptor complex. J Virol. 2014;88:3443-54 pubmed publisher
    ..Together, our findings implicate the endocytic machinery in the enhancement of HIV-1 infectivity by MLV glycoGag. ..
  52. Druck T, Gu Y, Prabhala G, Cannizzaro L, Park S, Huebner K, et al. Chromosome localization of human genes for clathrin adaptor polypeptides AP2 beta and AP50 and the clathrin-binding protein, VCP. Genomics. 1995;30:94-7 pubmed
    ..The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. ..
  53. Navarro Negredo P, Edgar J, Wrobel A, Zaccai N, Antrobus R, Owen D, et al. Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting. J Cell Biol. 2017;216:2927-2943 pubmed publisher
    ..In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell. ..