adaptor protein complex 3


Summary: An adaptor protein complex found primarily on perinuclear compartments.

Top Publications

  1. 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
  2. Harrison Lavoie K, Michaux G, Hewlett L, Kaur J, Hannah M, Lui Roberts W, et al. P-selectin and CD63 use different mechanisms for delivery to Weibel-Palade bodies. Traffic. 2006;7:647-62 pubmed
    ..Biogenesis of specialized organelles of haemopoietic cells is often adaptor protein complex 3-dependent (AP-3-dependent), and AP-3 has previously been shown to play a role in the trafficking of both ..
  3. Setty S, Tenza D, Truschel S, Chou E, Sviderskaya E, Theos A, et al. BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Mol Biol Cell. 2007;18:768-80 pubmed
  4. Pols M, Klumperman J. Trafficking and function of the tetraspanin CD63. Exp Cell Res. 2009;315:1584-92 pubmed publisher
    ..In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed. ..
  5. Rous B, Reaves B, Ihrke G, Briggs J, Gray S, Stephens D, et al. Role of adaptor complex AP-3 in targeting wild-type and mutated CD63 to lysosomes. Mol Biol Cell. 2002;13:1071-82 pubmed
    ..Using this AP-3-dependent mutant of CD63, we have shown that AP-3 functions in membrane traffic from the trans-Golgi network to lysosomes via an intracellular route that appears to bypass early endosomes. ..
  6. 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. ..
  7. 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
  8. Zlatic S, Tornieri K, L hernault S, Faundez V. Clathrin-dependent mechanisms modulate the subcellular distribution of class C Vps/HOPS tether subunits in polarized and nonpolarized cells. Mol Biol Cell. 2011;22:1699-715 pubmed publisher
    ..In addition, coats interact with membrane tethers required for vesicular fusion. The yeast AP-3 (Adaptor Protein Complex 3) coat and the class C Vps/HOPS (HOmotypic fusion and Protein Sorting) tether follow this model as their ..
  9. 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. ..

More Information


  1. 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. ..
  2. Progida C, Cogli L, Piro F, De Luca A, Bakke O, Bucci C. Rab7b controls trafficking from endosomes to the TGN. J Cell Sci. 2010;123:1480-91 pubmed publisher
    ..Altogether, these data indicate that Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN). ..
  3. Voglmaier S, Kam K, Yang H, Fortin D, Hua Z, Nicoll R, et al. Distinct endocytic pathways control the rate and extent of synaptic vesicle protein recycling. Neuron. 2006;51:71-84 pubmed
    ..After stimulation, however, inhibition of the AP3 pathway prevents the full recovery of VGLUT1 by endocytosis, implicating the AP3 pathway specifically in compensatory endocytosis. ..
  4. Wen W, Chen L, Wu H, Sun X, Zhang M, Banfield D. Identification of the yeast R-SNARE Nyv1p as a novel longin domain-containing protein. Mol Biol Cell. 2006;17:4282-99 pubmed
  5. Kural C, Tacheva Grigorova S, Boulant S, Cocucci E, Baust T, Duarte D, et al. Dynamics of intracellular clathrin/AP1- and clathrin/AP3-containing carriers. Cell Rep. 2012;2:1111-9 pubmed publisher
    ..This observation suggests that an alternative budding mechanism, yet to be discovered, is responsible for the scission step of clathrin/AP1 and clathrin/AP3 carriers...
  6. 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. ..
  7. Dong X, Li H, Derdowski A, Ding L, Burnett A, Chen X, et al. AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly. Cell. 2005;120:663-74 pubmed
    ..These studies illuminate an early step in retroviral particle assembly and provide evidence that the trafficking of Gag to late endosomes is part of a productive particle assembly pathway. ..
  8. 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...
  9. Muthusamy N, Faundez V, Bergson C. Calcyon, a mammalian specific NEEP21 family member, interacts with adaptor protein complex 3 (AP-3) and regulates targeting of AP-3 cargoes. J Neurochem. 2012;123:60-72 pubmed publisher
    ..Altogether, our data suggest that calcyon directly interacts with ?3A and ?3B, and regulates the subcellular distribution of AP-3 and the targeting of AP-3 cargoes. ..
  10. Newell Litwa K, Salazar G, Smith Y, Faundez V. Roles of BLOC-1 and adaptor protein-3 complexes in cargo sorting to synaptic vesicles. Mol Biol Cell. 2009;20:1441-53 pubmed publisher
    ..compartments where both selected synaptic vesicle and lysosomal membrane proteins coexist with the adaptor protein complex 3 (AP-3) in neuronal cells...
  11. Bultema J, Ambrosio A, Burek C, Di Pietro S. BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles. J Biol Chem. 2012;287:19550-63 pubmed publisher
    ..Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab32 has unique functions that cannot be carried out by Rab38 in melanosome biogenesis. ..
  12. Baust T, Anitei M, Czupalla C, Parshyna I, Bourel L, Thiele C, et al. Protein networks supporting AP-3 function in targeting lysosomal membrane proteins. Mol Biol Cell. 2008;19:1942-51 pubmed publisher
    ..This analysis reveals that these proteins, together with AP-3, play an essential role in protein sorting at early endosomes, thereby regulating the integrity of these organelles. ..
  13. Suzuki T, Orba Y, Makino Y, Okada Y, Sunden Y, Hasegawa H, et al. Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3. Proc Natl Acad Sci U S A. 2013;110:18668-73 pubmed publisher
    ..Here we demonstrate that the JCV agnoprotein specifically interacts with adaptor protein complex 3 through its ? subunit...
  14. Wei M. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 2006;19:19-42 pubmed
  15. Angers C, Merz A. HOPS interacts with Apl5 at the vacuole membrane and is required for consumption of AP-3 transport vesicles. Mol Biol Cell. 2009;20:4563-74 pubmed publisher
    ..We propose that AP-3 remains associated with budded vesicles, interacts with Vps41 and HOPS upon vesicle docking at the vacuole, and finally dissociates during docking or fusion. ..
  16. 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
    ..that VSV-G uses the tyrosine-based di-acidic motif (-YTDIE-) found in its cytoplasmic tail to recruit adaptor protein complex 3 for export from the trans-Golgi network...
  17. 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. ..
  18. 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...
  19. Salazar G, Craige B, Wainer B, Guo J, De Camilli P, Faundez V. Phosphatidylinositol-4-kinase type II alpha is a component of adaptor protein-3-derived vesicles. Mol Biol Cell. 2005;16:3692-704 pubmed
    ..Reduction of the cellular content of PI4KIIalpha strongly decreased the punctate distribution of AP-3 observed in PC12 cells. These results indicate that PI4KIIalpha is present on AP-3 organelles where it regulates AP-3 function. ..
  20. Anand V, Daboussi L, Lorenz T, Payne G. Genome-wide analysis of AP-3-dependent protein transport in yeast. Mol Biol Cell. 2009;20:1592-604 pubmed publisher
    ..We propose that the cargo-selective nature of the AP-3 pathway in yeast is achieved by AP-3 and Yck3p functioning in concert with machinery shared by other vacuolar transport pathways. ..
  21. Chapuy B, Tikkanen R, Mühlhausen C, Wenzel D, von Figura K, Honing S. AP-1 and AP-3 mediate sorting of melanosomal and lysosomal membrane proteins into distinct post-Golgi trafficking pathways. Traffic. 2008;9:1157-72 pubmed publisher
  22. 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...
  23. Bendor J, Lizardi Ortiz J, Westphalen R, Brandstetter M, Hemmings H, Sulzer D, et al. AGAP1/AP-3-dependent endocytic recycling of M5 muscarinic receptors promotes dopamine release. EMBO J. 2010;29:2813-26 pubmed publisher
    ..These results also suggest a novel therapeutic target for the treatment of dopaminergic dysfunction. ..
  24. Scheuber A, Rudge R, Danglot L, Raposo G, Binz T, Poncer J, et al. Loss of AP-3 function affects spontaneous and evoked release at hippocampal mossy fiber synapses. Proc Natl Acad Sci U S A. 2006;103:16562-7 pubmed
    ..We conclude that lack of AP-3 results in more constitutive secretion and loss of an asynchronous evoked release component, suggesting an important function of AP-3 in regulating SV exocytosis at MF terminals. ..
  25. Suzuki T, Matsubara Y, Kitani H, Ikeda H. Evaluation of the delta subunit of bovine adaptor protein complex 3 as a receptor for bovine leukaemia virus. J Gen Virol. 2003;84:1309-16 pubmed
    ..Many small insertions and deletions of nucleotides could generate the predicted transmembrane and cytoplasmic regions of the BLVR protein from the prototypic boAP3delta gene. ..
  26. Briken V, Jackman R, DasGupta S, Hoening S, Porcelli S. Intracellular trafficking pathway of newly synthesized CD1b molecules. EMBO J. 2002;21:825-34 pubmed
    ..Therefore, the intracellular trafficking of nascent CD1b via the cell surface to reach MIICs may allow the efficient sampling of lipid antigens present in endocytic compartments. ..
  27. Le Borgne R, Alconada A, Bauer U, Hoflack B. The mammalian AP-3 adaptor-like complex mediates the intracellular transport of lysosomal membrane glycoproteins. J Biol Chem. 1998;273:29451-61 pubmed
    ..These results provide evidence that AP-3 functions in the intracellular targeting of transmembrane glycoproteins to lysosomes. ..
  28. Medigeshi G, Schu P. Characterization of the in vitro retrograde transport of MPR46. Traffic. 2003;4:802-11 pubmed
    ..Residual membrane-associated AP-1 may have masked a requirement for cytosolic AP-1. The competence of membranes from AP-1-deficient cells for endosome-to-TGN transport in vitro was severely compromised. ..
  29. 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. ..
  30. 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. ..
  31. Larimore J, Tornieri K, Ryder P, Gokhale A, Zlatic S, Craige B, et al. The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell. 2011;22:4854-67 pubmed publisher
    ..into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route...
  32. Asensio C, Sirkis D, Edwards R. RNAi screen identifies a role for adaptor protein AP-3 in sorting to the regulated secretory pathway. J Cell Biol. 2010;191:1173-87 pubmed publisher
    ..Although vesicles with a dense core still form in the absence of AP-3, they contain substantially less synaptotagmin 1, indicating that AP-3 concentrates the proteins required for regulated exocytosis. ..
  33. Badolato R, Parolini S. Novel insights from adaptor protein 3 complex deficiency. J Allergy Clin Immunol. 2007;120:735-41; quiz 742-3 pubmed
    ..It is likely that the investigation of the physiopathology of Hermansky-Pudlak type 2 syndrome will reveal nonredundant functions of this adaptor protein in the intracellular trafficking of membrane proteins. ..
  34. Dell Angelica E. AP-3-dependent trafficking and disease: the first decade. Curr Opin Cell Biol. 2009;21:552-9 pubmed publisher
    ..These studies have brought into focus ideas about the specific roles of this pathway in protein trafficking and organelle biogenesis within the endosomal-lysosomal system...
  35. Rozenfeld R, Devi L. Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3. FASEB J. 2008;22:2311-22 pubmed publisher
    ..These results suggest that intracellular CB(1) receptors are functional and that their spatial segregation is likely to significantly affect receptor function. ..
  36. Rodionov D, Honing S, Silye A, Kongsvik T, von Figura K, Bakke O. Structural requirements for interactions between leucine-sorting signals and clathrin-associated adaptor protein complex AP3. J Biol Chem. 2002;277:47436-43 pubmed
    ..This is consistent with the suggested role of AP2 in internalization of proteins containing general leucine-based signals, including proteins that have been missorted to the plasma membrane. ..
  37. Salazar G, Love R, Werner E, Doucette M, Cheng S, Levey A, et al. The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted to a distinct synaptic vesicle subpopulation. Mol Biol Cell. 2004;15:575-87 pubmed
    ..Our evidence indicates that neuroendocrine cells assemble molecularly heterogeneous SV and suggests that this diversity could contribute to the functional variety of synapses. ..
  38. 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. ..
  39. 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. ..
  40. 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. ..
  41. 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. ..
  42. Berger A, Salazar G, Styers M, Newell Litwa K, Werner E, Maue R, et al. The subcellular localization of the Niemann-Pick Type C proteins depends on the adaptor complex AP-3. J Cell Sci. 2007;120:3640-52 pubmed
    ..These results provide information about how the NP-C proteins are targeted to their sites of action and illustrate the possibility that defective sorting of the NP-C proteins along the endocytic route can alter cellular cholesterol. ..
  43. Newell Litwa K, Seong E, Burmeister M, Faundez V. Neuronal and non-neuronal functions of the AP-3 sorting machinery. J Cell Sci. 2007;120:531-41 pubmed
    ..The heterotetrameric protein adaptor protein complex 3 (AP-3), a coat component, participates in the generation of a diverse group of secretory organelles and ..
  44. Martinez Arca S, Rudge R, Vacca M, Raposo G, Camonis J, Proux Gillardeaux V, et al. A dual mechanism controlling the localization and function of exocytic v-SNAREs. Proc Natl Acad Sci U S A. 2003;100:9011-6 pubmed
    ..Moreover, they point to the amino-terminal domains of SNARE proteins as multifunctional modules responsible for the fine tuning of SNARE function. ..
  45. Theos A, Tenza D, Martina J, Hurbain I, Peden A, Sviderskaya E, et al. Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. Mol Biol Cell. 2005;16:5356-72 pubmed
  46. Garcia E, Nikolic D, Piguet V. HIV-1 replication in dendritic cells occurs through a tetraspanin-containing compartment enriched in AP-3. Traffic. 2008;9:200-14 pubmed
  47. 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
  48. Shearman J, Wilton A. Elimination of neutrophil elastase and the genes for [corrected] adaptor protein complex 3 subunits [corrected] as the cause of trapped neutrophil syndrome in Border collies. Anim Genet. 2007;38:188-9 pubmed
  49. Salazar G, Craige B, Styers M, Newell Litwa K, Doucette M, Wainer B, et al. BLOC-1 complex deficiency alters the targeting of adaptor protein complex-3 cargoes. Mol Biol Cell. 2006;17:4014-26 pubmed
    ..These results indicate that the BLOC-1 and AP-3 protein complexes affect the targeting of SNARE and non-SNARE AP-3 cargoes and suggest a function of the BLOC-1 complex in membrane protein sorting. ..
  50. Janvier K, Kato Y, Boehm M, Rose J, Martina J, Kim B, et al. Recognition of dileucine-based sorting signals from HIV-1 Nef and LIMP-II by the AP-1 gamma-sigma1 and AP-3 delta-sigma3 hemicomplexes. J Cell Biol. 2003;163:1281-90 pubmed
    ..These observations reveal a novel mode of recognition of sorting signals involving the gamma/delta and sigma subunits of AP-1 and AP-3. ..
  51. Richmond B, Huizing M, Knapp J, Koshoffer A, Zhao Y, Gahl W, et al. Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking. J Invest Dermatol. 2005;124:420-7 pubmed
    ..These data demonstrate that the three initially identified subtypes of human HPS exhibit distinct defects in the trafficking of various melanocyte-specific proteins. ..
  52. Danglot L, Galli T. What is the function of neuronal AP-3?. Biol Cell. 2007;99:349-61 pubmed
    ..We propose that AP-3 plays an important regulatory role in neurons which contributes to the basal and stimulated exocytosis of synaptic vesicles. ..
  53. 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. ..