adaptor protein complex beta subunits


Summary: A family of large adaptin protein complex subunits of approximately 90-130 kDa in size.

Top Publications

  1. Nishimura N, Plutner H, Hahn K, Balch W. The delta subunit of AP-3 is required for efficient transport of VSV-G from the trans-Golgi network to the cell surface. Proc Natl Acad Sci U S A. 2002;99:6755-60 pubmed
  2. 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. ..
  3. 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. ..
  4. Peden A, Oorschot V, Hesser B, Austin C, Scheller R, Klumperman J. Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins. J Cell Biol. 2004;164:1065-76 pubmed
    ..Based on these data, we propose that AP-3 defines a novel pathway by which lysosomal membrane proteins are transported from tubular sorting endosomes to lysosomes. ..
  5. Kantheti P, Qiao X, Diaz M, Peden A, Meyer G, Carskadon S, et al. Mutation in AP-3 delta in the mocha mouse links endosomal transport to storage deficiency in platelets, melanosomes, and synaptic vesicles. Neuron. 1998;21:111-22 pubmed
    ..Our results demonstrate that the AP-3 complex is responsible for cargo selection to lysosome-related organelles such as melanosomes and platelet dense granules as well as to neurotransmitter vesicles. ..
  6. Kim Y, Benovic J. Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2 in G protein-coupled receptor trafficking. J Biol Chem. 2002;277:30760-8 pubmed
    ..These mutants should prove useful in better defining the role of arrestins in mediating receptor trafficking. ..
  7. Wenham M, Grieve S, Cummins M, Jones M, Booth S, Kilner R, et al. Two patients with Hermansky Pudlak syndrome type 2 and novel mutations in AP3B1. Haematologica. 2010;95:333-7 pubmed publisher
    ..These findings are consistent with CTL granule and platelet dense granule defects, respectively. This report extends the clinical and laboratory description of HPS2. ..
  8. 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. ..
  9. Seaman M, Sowerby P, Robinson M. Cytosolic and membrane-associated proteins involved in the recruitment of AP-1 adaptors onto the trans-Golgi network. J Biol Chem. 1996;271:25446-51 pubmed
    ..These proteins are all candidates for components of the adaptor docking site on the trans-Golgi network membrane. ..

More Information


  1. 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
  2. Owen D, Vallis Y, Pearse B, McMahon H, Evans P. The structure and function of the beta 2-adaptin appendage domain. EMBO J. 2000;19:4216-27 pubmed
    ..This results in the displacement of the other ligands from the beta 2 appendage. Thus clathrin binding to an AP2-accessory protein complex would cause the controlled release of accessory proteins at sites of vesicle formation. ..
  3. 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. ..
  4. Seong E, Wainer B, Hughes E, Saunders T, Burmeister M, Faundez V. Genetic analysis of the neuronal and ubiquitous AP-3 adaptor complexes reveals divergent functions in brain. Mol Biol Cell. 2005;16:128-40 pubmed
    ..Our results suggest that concerted nonredundant functions of neuronal and ubiquitous AP-3 provide a mechanism to control the levels of selected membrane proteins in synaptic vesicles. ..
  5. 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. ..
  6. Fontana S, Parolini S, Vermi W, Booth S, Gallo F, Donini M, et al. Innate immunity defects in Hermansky-Pudlak type 2 syndrome. Blood. 2006;107:4857-64 pubmed
    ..Taken together, these observations suggest that type 2 Hermansky-Pudlak syndrome is characterized by defects of innate immunity...
  7. Jung J, Bohn G, Allroth A, Boztug K, Brandes G, Sandrock I, et al. Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. Blood. 2006;108:362-9 pubmed
    ..Our findings extend the clinical and molecular phenotype of human AP-3 deficiency (also known as Hermansky-Pudlak syndrome, type 2) and provide further insights into the role of the AP-3 complex for the innate immune system...
  8. Gravotta D, Deora A, Perret E, Oyanadel C, Soza A, Schreiner R, et al. AP1B sorts basolateral proteins in recycling and biosynthetic routes of MDCK cells. Proc Natl Acad Sci U S A. 2007;104:1564-9 pubmed
    ..TfR utilizes a direct route from Golgi to basolateral membrane that is established as the epithelial monolayer matures. ..
  9. Wei M. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 2006;19:19-42 pubmed
  10. Clark R, Stinchcombe J, Day A, Blott E, Booth S, Bossi G, et al. Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse. Nat Immunol. 2003;4:1111-20 pubmed
    ..These data show that AP-3 is essential for polarized secretion from CTLs...
  11. Enders A, Zieger B, Schwarz K, Yoshimi A, Speckmann C, Knoepfle E, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. Blood. 2006;108:81-7 pubmed
    ..HPSII belongs to the group of familial hemophagocytic syndromes and may represent an indication for HSCT. ..
  12. He G, Gupta S, Yi M, Michaely P, Hobbs H, Cohen J. ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. J Biol Chem. 2002;277:44044-9 pubmed
    ..These data are consistent with the hypothesis that ARH functions as an adaptor protein that couples LDLR to the endocytic machinery. ..
  13. Laporte S, Miller W, Kim K, Caron M. beta-Arrestin/AP-2 interaction in G protein-coupled receptor internalization: identification of a beta-arrestin binging site in beta 2-adaptin. J Biol Chem. 2002;277:9247-54 pubmed
    ..These results suggest that the interaction of beta-arrestin with beta(2)-adaptin represents a selective endocytic trigger for several members of the GPCR family...
  14. Huizing M, Scher C, Strovel E, Fitzpatrick D, Hartnell L, Anikster Y, et al. Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2. Pediatr Res. 2002;51:150-8 pubmed
    ..Our findings expand the molecular, cellular, and clinical spectrum of HPS-2 and call for an increased index of suspicion for this diagnosis among patients with features of albinism, bleeding, and neutropenia. ..
  15. Nong Y, Huang Y, Ju W, Kalia L, Ahmadian G, Wang Y, et al. Glycine binding primes NMDA receptor internalization. Nature. 2003;422:302-7 pubmed
    ..Our results demonstrate transmembrane signal transduction through activating the glycine site of NMDARs, and elucidate a model for modulating cell-cell communication in the central nervous system. ..
  16. 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. ..
  17. Newman L, McKeever M, Okano H, Darnell R. Beta-NAP, a cerebellar degeneration antigen, is a neuron-specific vesicle coat protein. Cell. 1995;82:773-83 pubmed
    ..We propose a model in which beta-NAP mediates vesicle transport between the soma and the axon terminus and suggest that beta-NAP may represent a general class of coat proteins that mediates apical transport in polarized cells. ..
  18. Sirkis D, Edwards R, Asensio C. Widespread dysregulation of peptide hormone release in mice lacking adaptor protein AP-3. PLoS Genet. 2013;9:e1003812 pubmed publisher
    ..In addition, we show that loss of the related adaptor protein AP-1 has a similar effect on regulated secretion but exacerbates the effect of AP-3 RNAi, suggesting distinct roles for the two adaptors in the regulated secretory pathway. ..
  19. Poupart M, Fessart D, Cotton M, Laporte S, Claing A. ARF6 regulates angiotensin II type 1 receptor endocytosis by controlling the recruitment of AP-2 and clathrin. Cell Signal. 2007;19:2370-8 pubmed
    ..Taken together, these results suggest that the cycling of ARF6 between its GDP-and GTP-bound states coordinates the recruitment of AP-2 and clathrin to activated receptors during the endocytic process. ..
  20. Seroussi E, Kedra D, Pan H, Peyrard M, Schwartz C, Scambler P, et al. Duplications on human chromosome 22 reveal a novel Ret Finger Protein-like gene family with sense and endogenous antisense transcripts. Genome Res. 1999;9:803-14 pubmed
  21. Wong S, Santambrogio L, Strominger J. Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins. Proc Natl Acad Sci U S A. 2004;101:17783-8 pubmed
  22. Thornhill P, Cohn J, Drury G, Stanford W, Bernstein A, Desbarats J. A proteomic screen reveals novel Fas ligand interacting proteins within nervous system Schwann cells. FEBS Lett. 2007;581:4455-62 pubmed
    ..These proteins are all associated with endocytosis and trafficking, highlighting the tight regulation of cell surface expression of FasL in the nervous system. ..
  23. Dilaver G, Schepens J, van den Maagdenberg A, Wijers M, Pepers B, Fransen J, et al. Colocalisation of the protein tyrosine phosphatases PTP-SL and PTPBR7 with beta4-adaptin in neuronal cells. Histochem Cell Biol. 2003;119:1-13 pubmed
    ..Our data suggest that the tyrosine phosphatases PTP-SL and PTPBR7 may be involved in the formation and transport of AP4-coated vesicles or in the dephosphorylation of their transmembrane cargo molecules at or near the Golgi apparatus. ..
  24. Sasai M, Linehan M, Iwasaki A. Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science. 2010;329:1530-4 pubmed publisher
    ..Our results reveal an intracellular mechanism for bifurcation of TLR9 signals by selective receptor trafficking within the endosomal system...
  25. Huttenhower C, Haley E, Hibbs M, Dumeaux V, Barrett D, Coller H, et al. Exploring the human genome with functional maps. Genome Res. 2009;19:1093-106 pubmed publisher
    ..Our functional maps can be explored using HEFalMp (Human Experimental/Functional Mapper), a web interface allowing interactive visualization and investigation of this large body of information...
  26. Yao D, Ehrlich M, Henis Y, Leof E. Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit. Mol Biol Cell. 2002;13:4001-12 pubmed
  27. Takahashi D, Hase K, Kimura S, Nakatsu F, Ohmae M, Mandai Y, et al. The epithelia-specific membrane trafficking factor AP-1B controls gut immune homeostasis in mice. Gastroenterology. 2011;141:621-32 pubmed publisher
    ..The AP-1B-mediated protein sorting machinery is required for maintenance of immune homeostasis and prevention of excessive inflammation. ..
  28. Dong H, Yuan H, Jin W, Shen Y, Xu X, Wang H. Involvement of beta3A subunit of adaptor protein-3 in intracellular trafficking of receptor-like protein tyrosine phosphatase PCP-2. Acta Biochim Biophys Sin (Shanghai). 2007;39:540-6 pubmed
    ..Our results suggested a possible mechanism of intracellular trafficking of PCP-2 mediated by AP-3 and SNX3 which might participate in the regulation of PCP-2 functions. ..
  29. Zhang X, Yin L, Zheng Y, Lu L, Zhou Z, Sha J. Expression of a novel beta adaptin subunit mRNA splice variant in human testes. Asian J Androl. 2005;7:179-88 pubmed
    ..Ap2beta-NY is an isoform of Ap2beta and may be involved in regulating the process of spermatogenesis and testis development. ..
  30. Han L, Campanucci V, Cooke J, Salter M. Identification of a single amino acid in GluN1 that is critical for glycine-primed internalization of NMDA receptors. Mol Brain. 2013;6:36 pubmed publisher
    ..Moreover, we have demonstrated the principle that while NMDA receptor gating and priming share a common requirement for glycine binding, the molecular constraints in GluN1 for gating are distinct from those for priming. ..
  31. Newell Litwa K, Chintala S, Jenkins S, Pare J, McGaha L, Smith Y, et al. Hermansky-Pudlak protein complexes, AP-3 and BLOC-1, differentially regulate presynaptic composition in the striatum and hippocampus. J Neurosci. 2010;30:820-31 pubmed publisher
    ..We propose that anatomically restricted mechanisms within the brain diversify the biogenesis and composition of synaptic vesicles. ..
  32. Weixel K, Bradbury N. Endocytic adaptor complexes bind the C-terminal domain of CFTR. Pflugers Arch. 2001;443 Suppl 1:S70-4 pubmed
    ..Thus, we demonstrate that CFTR is endocytosed via clathrin-coated vesicles, and that targeting of CFTR to these structures is mediated by binding of the AP-2 adaptor complex to the C-terminal domain of CFTR. ..
  33. Chen C, Zou X, Ji C, Zhao S, Lv L, Gu S, et al. Characterization of AP3B2_v2, a novel splice variant of human AP3B2. DNA Seq. 2007;18:165-8 pubmed
    ..The expression levels of AP3B2_v2 were relatively high in brain and testis. In contrast, low levels of expression were detected in kidney, pancreas, spleen, thymus, prostate, ovary and small intestine. ..
  34. Nikawa J, Yata M, Motomura M, Miyoshi N, Ueda T, Hisada D. Ternary complex formation of Ino2p-Ino4p transcription factors and Apl2p adaptin beta subunit in yeast. Biosci Biotechnol Biochem. 2006;70:2604-12 pubmed
    ..These results indicate a genetic interaction between APL2, INO2 and INO4 and uncovere novel functions of the Ino2p-Ino4p-Apl2p complex in yeast. ..
  35. Schmid E, Ford M, Burtey A, Praefcke G, Peak Chew S, Mills I, et al. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006;4:e262 pubmed
    ..However, proteins such as beta-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors...
  36. Kim Y, Barak L, Caron M, Benovic J. Regulation of arrestin-3 phosphorylation by casein kinase II. J Biol Chem. 2002;277:16837-46 pubmed
    ..Differences between the regulatory roles of arrestin-2 and -3 phosphorylation may contribute to the different cellular functions of these proteins in G protein-coupled receptor signaling and regulation. ..
  37. Geyer M, Fackler O, Peterlin B. Subunit H of the V-ATPase involved in endocytosis shows homology to beta-adaptins. Mol Biol Cell. 2002;13:2045-56 pubmed
    ..Based on recent structural analysis, our results suggest that the di-leucine-binding domain consists of a HEAT or ARM repeat protein fold. ..
  38. Dell Angelica E, Ooi C, Bonifacino J. Beta3A-adaptin, a subunit of the adaptor-like complex AP-3. J Biol Chem. 1997;272:15078-84 pubmed
    ..The characteristics of beta3A-adaptin reported here lend support to the idea that AP-3 is a structural and functional homolog of the clathrin-associated adaptors AP-1 and AP-2. ..
  39. Brandhorst T, Rooney P, Sullivan T, Klein B. Using new genetic tools to study the pathogenesis of Blastomyces dermatitidis. Trends Microbiol. 2002;10:25-30 pubmed
  40. Deloche O, Yeung B, Payne G, Schekman R. Vps10p transport from the trans-Golgi network to the endosome is mediated by clathrin-coated vesicles. Mol Biol Cell. 2001;12:475-85 pubmed
    ..The Vps10p C-terminal domain appears to play a principal role in retrieval of Vps10p from the prevacuolar compartment rather than in sorting from the TGN...
  41. 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. ..
  42. Palmer C, Lim W, Hastie P, Toward M, Korolchuk V, Burbidge S, et al. Hippocalcin functions as a calcium sensor in hippocampal LTD. Neuron. 2005;47:487-94 pubmed
    ..These data indicate that the AP2-hippocalcin complex acts as a Ca(2+) sensor that couples NMDAR-dependent activation to regulated endocytosis of AMPARs during LTD. ..
  43. Peyrard M, Fransson I, Xie Y, Han F, Ruttledge M, Swahn S, et al. Characterization of a new member of the human beta-adaptin gene family from chromosome 22q12, a candidate meningioma gene. Hum Mol Genet. 1994;3:1393-9 pubmed
    ..Based on this, we propose BAM22 as a second chromosome 22 locus important in meningioma development, after the neurofibromatosis type 2 gene. ..
  44. Camidge D, Pearse B. Cloning of Drosophila beta-adaptin and its localization on expression in mammalian cells. J Cell Sci. 1994;107 ( Pt 3):709-18 pubmed
    ..Four of these (one with respect to beta and three versus 105a) are clustered in a particular region (residues 155 to 305), which may therefore represent a domain that influences the choice of partner adaptin. ..
  45. Gwynn B, Martina J, Bonifacino J, Sviderskaya E, Lamoreux M, Bennett D, et al. Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex. Blood. 2004;104:3181-9 pubmed
    ..Defects in all the 5 known components of BLOC-1, including RP, cause severe HPS in mice, suggesting that the subunits are nonredundant and that BLOC-1 plays a key role in organelle biogenesis. ..
  46. Ricotta D, Hansen J, Preiss C, Teichert D, Honing S. Characterization of a protein phosphatase 2A holoenzyme that dephosphorylates the clathrin adaptors AP-1 and AP-2. J Biol Chem. 2008;283:5510-7 pubmed
  47. Rudinskiy N, Grishchuk Y, Vaslin A, Puyal J, Delacourte A, Hirling H, et al. Calpain hydrolysis of alpha- and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration. J Biol Chem. 2009;284:12447-58 pubmed publisher
  48. Morgan G, Allen C, Jeffries T, Hollinshead M, Field M. Developmental and morphological regulation of clathrin-mediated endocytosis in Trypanosoma brucei. J Cell Sci. 2001;114:2605-15 pubmed
    ..Modulation of clathrin expression is likely to be an important factor in the developmental regulation of endocytosis and recycling in the African trypanosome. ..
  49. Jessen B, Bode S, Ammann S, Chakravorty S, Davies G, Diestelhorst J, et al. The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. Blood. 2013;121:2943-51 pubmed publisher
    ..HPS2 confers a risk for HLH that is lower than in Griscelli or Chediak-Higashi syndrome, probably because of a milder defect in cytotoxicity. Preemptive hematopoietic stem cell transplantation does not appear justified in HPS2. ..
  50. Greenberg M, Bronson S, Lock M, Neumann M, Pavlakis G, Skowronski J. Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation. EMBO J. 1997;16:6964-76 pubmed
    ..This evidence supports a model whereby Nef recruits CD4 to the endocytic machinery via AP-2-containing clathrin coats at the plasma membrane. ..
  51. Laporte S, Oakley R, Zhang J, Holt J, Ferguson S, Caron M, et al. The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc Natl Acad Sci U S A. 1999;96:3712-7 pubmed
    ..These findings point to a role for AP-2 in GPCR endocytosis, and they suggest that AP-2 functions as a clathrin adaptor for the endocytosis of diverse classes of membrane receptors. ..
  52. Yang W, Li C, Ward D, Kaplan J, Mansour S. Defective organellar membrane protein trafficking in Ap3b1-deficient cells. J Cell Sci. 2000;113 ( Pt 22):4077-86 pubmed
    ..In particular, the Lamp proteins were clustered on the cell surface. These findings strengthen the evidence for an alternate pathway via the plasma membrane for cargo normally transported to organelles by AP-3. ..
  53. Lyerla T, Rusiniak M, Borchers M, Jahreis G, Tan J, Ohtake P, et al. Aberrant lung structure, composition, and function in a murine model of Hermansky-Pudlak syndrome. Am J Physiol Lung Cell Mol Physiol. 2003;285:L643-53 pubmed
    ..These mutant mice provide a model to further investigate the lung pathology and therapy of HPS. We hypothesize that abnormal type II cell lamellar body structure/function may predict future lung pathology in HPS...