adaptor protein complex alpha subunits


Summary: A family of large adaptin protein subunits of approximately 100 kDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 2.

Top Publications

  1. Rosenthal J, Chen H, Slepnev V, Pellegrini L, Salcini A, Di Fiore P, et al. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module. J Biol Chem. 1999;274:33959-65 pubmed
    ..The epsins define a new protein family implicated in membrane dynamics at the cell surface. ..
  2. 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. ..
  3. Hirst J, Robinson M. Clathrin and adaptors. Biochim Biophys Acta. 1998;1404:173-93 pubmed
    ..Genetic studies indicate that AP-3 plays a role in the sorting of proteins to lysosomes and lysosome-related organelles. ..
  4. Slepnev V, Ochoa G, Butler M, Grabs D, De Camilli P. Role of phosphorylation in regulation of the assembly of endocytic coat complexes. Science. 1998;281:821-4 pubmed
    ..Thus, phosphorylation regulates the association and dissociation cycle of the clathrin-based endocytic machinery, and calcium-dependent dephosphorylation of endocytic proteins could prepare nerve terminals for a burst of endocytosis. ..
  5. Hussain N, Yamabhai M, Ramjaun A, Guy A, Baranes D, O Bryan J, et al. Splice variants of intersectin are components of the endocytic machinery in neurons and nonneuronal cells. J Biol Chem. 1999;274:15671-7 pubmed
    ..These data suggest that the long and short forms of intersectin are components of the endocytic machinery in neurons and nonneuronal cells. ..
  6. Klumperman J, Kuliawat R, Griffith J, Geuze H, Arvan P. Mannose 6-phosphate receptors are sorted from immature secretory granules via adaptor protein AP-1, clathrin, and syntaxin 6-positive vesicles. J Cell Biol. 1998;141:359-71 pubmed
    ..Thus, we hypothesize that during secretory granule maturation, MPR-ligand complexes and syntaxin 6 are removed from IGs by AP-1/clathrin-coated vesicles, and then delivered to endosomes. ..
  7. Okabayashi Y, Sugimoto Y, Totty N, Hsuan J, Kido Y, Sakaguchi K, et al. Interaction of Shc with adaptor protein adaptins. J Biol Chem. 1996;271:5265-9 pubmed
    ..Thus, this study indicates the specific interaction of Shc with alpha- and beta-adaptin components of plasma membrane adaptor proteins that are thought to be involved in receptor endocytosis. ..
  8. Benmerah A, Gagnon J, Begue B, Megarbane B, Dautry Varsat A, Cerf Bensussan N. The tyrosine kinase substrate eps15 is constitutively associated with the plasma membrane adaptor AP-2. J Cell Biol. 1995;131:1831-8 pubmed
  9. Sorkin A, Carpenter G. Interaction of activated EGF receptors with coated pit adaptins. Science. 1993;261:612-5 pubmed
    ..The extent of receptor-adaptin association was increased in cells depleted of potassium to block endocytosis. These data suggest that receptor-adaptin association occurs in intact cells before coated pits are fully assembled. ..

More Information


  1. Martina J, Bonangelino C, Aguilar R, Bonifacino J. Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery. J Cell Biol. 2001;153:1111-20 pubmed
    ..These observations suggest that stonin 2 is a novel component of the general endocytic machinery. ..
  2. Ball C, Hunt S, Robinson M. Expression and localization of alpha-adaptin isoforms. J Cell Sci. 1995;108 ( Pt 8):2865-75 pubmed
    ..This suggests that alpha C may play more of a role in the recycling of membrane components throughout the cell. ..
  3. 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. ..
  4. Santini F, Marks M, Keen J. Endocytic clathrin-coated pit formation is independent of receptor internalization signal levels. Mol Biol Cell. 1998;9:1177-94 pubmed
    ..Rather, the findings support a model in which coated pit formation proceeds through recruitment and activation of AP2, likely through a limited number of regulated docking sites that act independently of endocytic signals...
  5. Seaman M, Ball C, Robinson M. Targeting and mistargeting of plasma membrane adaptors in vitro. J Cell Biol. 1993;123:1093-105 pubmed
    ..Intracellular sequestration of PM adaptor receptors may provide the cell with a mechanism for up-regulating endocytosis following a burst of exocytosis. ..
  6. 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. ..
  7. Schledzewski K, Brinkmann H, Mendel R. Phylogenetic analysis of components of the eukaryotic vesicle transport system reveals a common origin of adaptor protein complexes 1, 2, and 3 and the F subcomplex of the coatomer COPI. J Mol Evol. 1999;48:770-8 pubmed
    ..The situation encountered today is the result of successive rounds of coordinated gene duplications of both the large and the small/medium subunits, with F-COPI being the first that separated from the ancestral pre-F-COPI...
  8. Dornan S, Jackson A, Gay N. Alpha-adaptin, a marker for endocytosis, is expressed in complex patterns during Drosophila development. Mol Biol Cell. 1997;8:1391-403 pubmed
    ..Taken together with previous evidence, our results suggest that endosomal vesicle trafficking, membrane recycling, and the regulation of endocytosis play critical roles in the wide range of developmental processes. ..
  9. Littleton J, Bai J, Vyas B, Desai R, Baltus A, Garment M, et al. synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+-triggered fusion and recycling of synaptic vesicles in vivo. J Neurosci. 2001;21:1421-33 pubmed
    ..These data suggest that Ca(2+)-driven oligomerization via the C2B domain of synaptotagmin may trigger synaptic vesicle fusion via the assembly and clustering of SNARE complexes. ..
  10. Chang M, Mallet W, Mostov K, Brodsky F. Adaptor self-aggregation, adaptor-receptor recognition and binding of alpha-adaptin subunits to the plasma membrane contribute to recruitment of adaptor (AP2) components of clathrin-coated pits. EMBO J. 1993;12:2169-80 pubmed
  11. Kirchhausen T. Adaptors for clathrin-mediated traffic. Annu Rev Cell Dev Biol. 1999;15:705-32 pubmed
    ..This review focuses on the most recent advances dealing with the molecular basis for sorting by clathrin adaptors...
  12. Owen D, Luzio J. Structural insights into clathrin-mediated endocytosis. Curr Opin Cell Biol. 2000;12:467-74 pubmed
    ..Recent atomic resolution structures determined by X-ray crystallography now enable the molecular basis for the interactions of some components of the endocytic machinery to be understood in detail. ..
  13. Boehm M, Bonifacino J. Adaptins: the final recount. Mol Biol Cell. 2001;12:2907-20 pubmed
    ..Finally, we extend our survey to adaptin-related proteins such as the GGAs and stonins, which contain domains homologous to the adaptins. ..
  14. Berdnik D, Torok T, Gonzalez Gaitan M, Knoblich J. The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell division in Drosophila. Dev Cell. 2002;3:221-31 pubmed
    ..Our results suggest a model in which Numb influences cell fate by downregulating Notch through polarized receptor-mediated endocytosis, since Numb also binds to the intracellular domain of Notch. ..
  15. Dell Angelica E, Mullins C, Bonifacino J. AP-4, a novel protein complex related to clathrin adaptors. J Biol Chem. 1999;274:7278-85 pubmed
    ..We propose that, like the related AP-1, AP-2, and AP-3 complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells. ..
  16. Ponnambalam S, Robinson M, Jackson A, Peiperl L, Parham P. Conservation and diversity in families of coated vesicle adaptins. J Biol Chem. 1990;265:4814-20 pubmed
    ..The structures of the beta and alpha adaptins can both be divided into two globular domains interconnected by a variable and potentially flexible stalk domain. ..
  17. Nakagawa T, Setou M, Seog D, Ogasawara K, Dohmae N, Takio K, et al. A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell. 2000;103:569-81 pubmed
    ..Functional blockade of KIF13A reduced cell surface expression of the M6PR. Thus, KIF13A transports M6PR-containing vesicles and targets the M6PR from TGN to the plasma membrane via direct interaction with the AP-1 adaptor complex. ..
  18. Wigge P, Vallis Y, McMahon H. Inhibition of receptor-mediated endocytosis by the amphiphysin SH3 domain. Curr Biol. 1997;7:554-60 pubmed
    ..We propose that amphiphysin is not only required for synaptic-vesicle endocytosis, but might also be a key player in dynamin recruitment in all cells undergoing receptor-mediated endocytosis. ..
  19. 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. ..
  20. Chen H, Slepnev V, Di Fiore P, De Camilli P. The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation in nerve terminals. J Biol Chem. 1999;274:3257-60 pubmed
  21. Santolini E, Puri C, Salcini A, Gagliani M, Pelicci P, Tacchetti C, et al. Numb is an endocytic protein. J Cell Biol. 2000;151:1345-52 pubmed
    ..Finally, fragments of Numb act as dominant negatives on both constitutive and ligand-regulated receptor-mediated internalization, suggesting a general role for Numb in the endocytic process. ..
  22. Slepnev V, De Camilli P. Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nat Rev Neurosci. 2000;1:161-72 pubmed
    ..This review summarizes these advances with a special focus on accessory factors and highlights new aspects of clathrin-mediated endocytosis revealed by the study of these factors. ..
  23. Takatsu H, Sakurai M, Shin H, Murakami K, Nakayama K. Identification and characterization of novel clathrin adaptor-related proteins. J Biol Chem. 1998;273:24693-700 pubmed
    ..These data suggest that gamma2-adaptin constitute a novel adaptor-related complex that participates in a transport step different from that of AP-1. ..
  24. 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. ..
  25. Chen H, Fre S, Slepnev V, Capua M, Takei K, Butler M, et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature. 1998;394:793-7 pubmed
    ..We propose that epsin may participate, together with Eps15, in the molecular rearrangement of the clathrin coats that are required for coated-pit invagination and vesicle fission. ..
  26. Owen D, Vallis Y, Noble M, Hunter J, Dafforn T, Evans P, et al. A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain. Cell. 1999;97:805-15 pubmed
    ..A single site for binding multiple ligands would allow for temporal and spatial regulation in the recruitment of components of the endocytic machinery. ..
  27. Haucke V, De Camilli P. AP-2 recruitment to synaptotagmin stimulated by tyrosine-based endocytic motifs. Science. 1999;285:1268-71 pubmed
    ..This suggests a mechanism by which nucleation of clathrin-coated pits is stimulated by the loading of cargo proteins...
  28. Matter K. Epithelial polarity: sorting out the sorters. Curr Biol. 2000;10:R39-42 pubmed
    ..While various sorting signals and pathways have been identified, only recently has a protein been identified that recognizes such sorting determinants and mediates sorting to a specific cell-surface domain. ..
  29. Eugster A, Frigerio G, Dale M, Duden R. COP I domains required for coatomer integrity, and novel interactions with ARF and ARF-GAP. EMBO J. 2000;19:3905-17 pubmed
    ..Glo3p also interacts with intact coatomer in vitro. ..
  30. Robinson M. Cloning of cDNAs encoding two related 100-kD coated vesicle proteins (alpha-adaptins). J Cell Biol. 1989;108:833-42 pubmed
    ..Antipeptide antibodies are now being raised to find out whether the proteins are localized in functionally distinct populations of endocytic coated vesicles. ..
  31. David C, McPherson P, Mundigl O, De Camilli P. A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc Natl Acad Sci U S A. 1996;93:331-5 pubmed
    ..These findings support a role of amphiphysin in synaptic vesicle endocytosis. ..
  32. Benmerah A, Begue B, Dautry Varsat A, Cerf Bensussan N. The ear of alpha-adaptin interacts with the COOH-terminal domain of the Eps 15 protein. J Biol Chem. 1996;271:12111-6 pubmed
    ..Our data indicate that this specific part of AP-2 binds to a cellular component and provide the tools for investigating the functions of the association between AP-2 and Eps15. ..
  33. Gaidarov I, Keen J. Phosphoinositide-AP-2 interactions required for targeting to plasma membrane clathrin-coated pits. J Cell Biol. 1999;146:755-64 pubmed
    ..1999. EMBO (Eur. Mol. Biol. Organ.) J. 18:871-881), suggest that phosphoinositides play a critical and general role in adaptor incorporation into plasma membrane clathrin-coated pits...
  34. Leprince C, Romero F, Cussac D, Vayssiere B, Berger R, Tavitian A, et al. A new member of the amphiphysin family connecting endocytosis and signal transduction pathways. J Biol Chem. 1997;272:15101-5 pubmed
    ..This hypothesis is strengthened by the ability of BRAMP2 to interact with the p21(ras) exchange factor SOS, in vitro, as a possible point of interconnection between the endocytic and signaling pathways. ..
  35. 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...
  36. Gonzalez Gaitan M, Jackle H. Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell. 1997;88:767-76 pubmed
    ..Our results suggest an alpha-adaptin-dependent control of the vesicle cycle that maintains the balance between the amount of vesicle- and surface-associated membranes. ..
  37. Roos J, Kelly R. Dap160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin. J Biol Chem. 1998;273:19108-19 pubmed
    ..We suggest that Dap160 is a scaffolding protein that helps anchor proteins required for endocytosis at sites where they are needed in the Drosophila nerve terminal. ..
  38. Wan L, Molloy S, Thomas L, Liu G, Xiang Y, Rybak S, et al. PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell. 1998;94:205-16 pubmed
    ..Cell-free assays indicate TGN localization of furin is directed by a PACS-1-mediated retrieval step. Together, these findings explain a mechanism by which membrane proteins in mammalian cells are localized to the TGN. ..
  39. Morris S, Cooper J. Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2. Traffic. 2001;2:111-23 pubmed
    ..These findings suggest that in addition to previously reported signal-transduction functions, Dab2 could also act as an adaptor protein that may regulate protein trafficking...
  40. 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. ..
  41. Kreuzer O, Krisch B, Dery O, Bunnett N, Meyerhof W. Agonist-mediated endocytosis of rat somatostatin receptor subtype 3 involves beta-arrestin and clathrin coated vesicles. J Neuroendocrinol. 2001;13:279-87 pubmed
    ..Thus, agonist-induced endocytosis of sst3 depends on its interaction with beta-arrestin, involves the adaptor protein complex 2 and proceeds via clathrin coated vesicles to the recycling compartment...
  42. Smith C, Grigorieff N, Pearse B. Clathrin coats at 21 A resolution: a cellular assembly designed to recycle multiple membrane receptors. EMBO J. 1998;17:4943-53 pubmed
    ..The inter-subunit interactions visible in this map provide a structural basis for considering the assembly of clathrin coats on a membrane and show the contacts which will need to be disrupted during disassembly. ..
  43. Chen G, Masana M, Manji H. Lithium regulates PKC-mediated intracellular cross-talk and gene expression in the CNS in vivo. Bipolar Disord. 2000;2:217-36 pubmed
    ..Together, these results suggest that the PKC signaling pathway and PKC-mediated gene expression may be important mediators of lithium's long-term therapeutic effects in a disorder as complex as BD...
  44. 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. ..
  45. Berlioz Torrent C, Shacklett B, Erdtmann L, Delamarre L, Bouchaert I, Sonigo P, et al. Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins. J Virol. 1999;73:1350-61 pubmed
  46. Denisov A, Ritter B, McPherson P, Gehring K. 1H, 15N and 13C resonance assignments and 15N-1H residual dipolar couplings for the alpha-adaptin ear-domain. J Biomol NMR. 2004;29:441-2 pubmed
  47. Miralles F, Parra M, Caelles C, Nagamine Y, Felez J, Munoz Canoves P. UV irradiation induces the murine urokinase-type plasminogen activator gene via the c-Jun N-terminal kinase signaling pathway: requirement of an AP1 enhancer element. Mol Cell Biol. 1998;18:4537-47 pubmed
    ..This activation links external UV stimulation and AP1-dependent uPA transcription, providing a transcription-coupled signal transduction pathway for the induction of the murine uPA gene by UV. ..
  48. Mullins C, Bonifacino J. The molecular machinery for lysosome biogenesis. Bioessays. 2001;23:333-43 pubmed
    ..Other recently identified components, however, appear to be unique to higher eukaryotes. BioEssays 23:333-343, 2001. Published 2001 John Wiley & Sons, Inc. ..
  49. Yamazaki T, Koo E, Selkoe D. Cell surface amyloid beta-protein precursor colocalizes with beta 1 integrins at substrate contact sites in neural cells. J Neurosci. 1997;17:1004-10 pubmed
    ..These results are consistent with the putative role of beta PP in cell adhesion and suggests that beta PP either interacts with selected integrins or shares similar cellular machinery to promote cell adhesion. ..
  50. Rabouille C, Kuntz D, Lockyer A, Watson R, Signorelli T, Rose D, et al. The Drosophila GMII gene encodes a Golgi alpha-mannosidase II. J Cell Sci. 1999;112 ( Pt 19):3319-30 pubmed
    ..We discuss these results in terms of the possible use of dGMII as a Drosophila Golgi marker. ..
  51. Sato M, Sato K, Fonarev P, Huang C, Liou W, Grant B. Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit. Nat Cell Biol. 2005;7:559-69 pubmed
    ..These results suggest a mechanism for the activation of Rab5 in clathrin-coated pits or clathrin-coated vesicles that is essential for the delivery of endocytic cargo to early endosomes...
  52. Kang Decker N, Mantchev G, Juneja S, McNiven M, van Deursen J. Lack of acrosome formation in Hrb-deficient mice. Science. 2001;294:1531-3 pubmed
    ..We conclude that Hrb is required for docking and/or fusion of proacrosomic vesicles during acrosome biogenesis. ..
  53. Mullins C, Hartnell L, Wassarman D, Bonifacino J. Defective expression of the mu3 subunit of the AP-3 adaptor complex in the Drosophila pigmentation mutant carmine. Mol Gen Genet. 1999;262:401-12 pubmed
    ..These findings provide evidence of a role for mu3 in the sorting processes required for pigment granule biogenesis in Drosophila. ..