Genomes and Genes
Gene Symbol: AP-2alpha
Description: Adaptor Protein complex 2, alpha subunit
Alias: AP-2, AP2, Ada, Alpha-Adaptin, CG31654, CG4260, D-Ada, D-alphaAda, Dmel\CG4260, MENE (2L)-A, MENE(2L)-A, ada, alpha, alpha-Ada, alpha-Adaptin, alpha-ada, alpha-adaptin, alphaAda, apl3, cg4260, dAP-2a, l(2)06694, l(2)SH0460, l(2)SH2 0460, adaptor protein complex 2, alpha subunit, AP-2alpha-PA, AP-2alpha-PB, Alpha-adaptin, CG4260-PA, CG4260-PB, alpha adaptin, alphaAdaptin, lethal (2) SH0460
Species: fruit fly
- Hutterer A, Knoblich J. Numb and alpha-Adaptin regulate Sanpodo endocytosis to specify cell fate in Drosophila external sensory organs. EMBO Rep. 2005;6:836-42 pubmed..Sanpodo endocytosis requires alpha-Adaptin, a Numb-binding partner involved in clathrin-mediated endocytosis...
- Cayouette M, Raff M. Asymmetric segregation of Numb: a mechanism for neural specification from Drosophila to mammals. Nat Neurosci. 2002;5:1265-9 pubmed..Here, we review these and other findings that suggest an important role for the asymmetric segregation of Numb proteins in vertebrate neural development. ..
- Windler S, Bilder D. Endocytic internalization routes required for delta/notch signaling. Curr Biol. 2010;20:538-43 pubmed publisher..The absolute requirement for dynamin-dependent endocytosis but not endosomal entry or Rab11 activity supports "pulling force" rather than "recycling" models for Delta activation. ..
- Justice N, Roegiers F, Jan L, Jan Y. Lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the Drosophila adult sensory organ precursor lineage. Curr Biol. 2003;13:778-83 pubmed..These findings uncover a previously unknown function of Lgl in the inhibition of Notch and reveal different modes of action by which Lgl can influence cell fate in the neuroblast and SOP lineages. ..
- Khuong T, Habets R, Kuenen S, Witkowska A, Kasprowicz J, Swerts J, et al. Synaptic PI(3,4,5)P3 is required for Syntaxin1A clustering and neurotransmitter release. Neuron. 2013;77:1097-108 pubmed publisher..Thus, our data indicate that PI(3,4,5)P3, based on electrostatic interactions, clusters Syntaxin1A at release sites to regulate neurotransmitter release. ..
- Compagnon J, Gervais L, Roman M, Chamot Boeuf S, Guichet A. Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in the Drosophila germline. J Cell Sci. 2009;122:25-35 pubmed publisher..Hence, our results argue strongly in favor of the hypothesis that the Rab5-dependant release of PtdIns(4,5)P(2) from endosomes that we discovered in this study is crucial for endocytosis to proceed. ..
- Sommer B, Oprins A, Rabouille C, Munro S. The exocyst component Sec5 is present on endocytic vesicles in the oocyte of Drosophila melanogaster. J Cell Biol. 2005;169:953-63 pubmed..Thus, the exocyst may act in both Golgi to plasma membrane traffic and endocytic cycling, and hence in oocytes is recruited to clathrin-coated pits to facilitate the rapid recycling of Yolkless. ..
- Majumdar A, Ramagiri S, Rikhy R. Drosophila homologue of Eps15 is essential for synaptic vesicle recycling. Exp Cell Res. 2006;312:2288-98 pubmed..Eps15 mutants show a decrease in the alpha-Adaptin levels at the larval neuromuscular junction synapse...
- Gonzalez Gaitan M, Jackle H. Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell. 1997;88:767-76 pubmed..nervous system involves presynaptic vesicle recycling by clathrin-mediated endocytosis, an event triggered by the alpha-adaptin-containing AP2 complex...
- Lee D, Harris T. An Arf-GEF regulates antagonism between endocytosis and the cytoskeleton for Drosophila blastoderm development. Curr Biol. 2013;23:2110-20 pubmed publisher..Endocytosis also regulates the PM and can be promoted or inhibited by cytoskeletal networks. However, endocytic regulation of the general membrane cytoskeleton is undocumented...
- Wu M, Bellen H. Genetic dissection of synaptic transmission in Drosophila. Curr Opin Neurobiol. 1997;7:624-30 pubmed..In addition, characterization of Drosophila endocytotic mutants provides in vivo evidence for the presence of different endocytotic pathways at a single synapse. ..
- Guha A, Sriram V, Krishnan K, Mayor S. Shibire mutations reveal distinct dynamin-independent and -dependent endocytic pathways in primary cultures of Drosophila hemocytes. J Cell Sci. 2003;116:3373-86 pubmed..temperature in shits cells, receptor-bound ALs remain completely surface accessible, localized to clathrin and alpha-adaptin-positive structures...
- Halbsgut N, Linnemannstöns K, Zimmermann L, Wodarz A. Apical-basal polarity in Drosophila neuroblasts is independent of vesicular trafficking. Mol Biol Cell. 2011;22:4373-9 pubmed publisher..Surprisingly, we found that none of these mutations affected NB polarity, demonstrating that NB cortical polarity is independent of plasma membrane polarity and that the PAR proteins function in a cell type-specific manner. ..
- Herz H, Madden L, Chen Z, Bolduc C, Buff E, Gupta R, et al. The H3K27me3 demethylase dUTX is a suppressor of Notch- and Rb-dependent tumors in Drosophila. Mol Cell Biol. 2010;30:2485-97 pubmed publisher..In summary, these data suggest that dUTX is a suppressor of Notch- and Rbf-dependent tumors in Drosophila melanogaster and may provide a model for UTX-dependent tumorigenesis in humans. ..
- Cadavid A, Ginzel A, Fischer J. The function of the Drosophila fat facets deubiquitinating enzyme in limiting photoreceptor cell number is intimately associated with endocytosis. Development. 2000;127:1727-36 pubmed..Moreover, it is demonstrated that the fat facets mutant phenotype is extraordinarily sensitive to the level of liquid facets expression. We propose that Liquid facets is a candidate for the critical substrate of Fat facets in the eye. ..
- Carthew R, Xu C. Endocytosis: why not wait to deubiquitinate?. Curr Biol. 2000;10:R532-4 pubmed..Surprisingly, this is the opposite effect that ubiquitination has on endocytosis of many plasma membrane proteins. ..
- Li X, Kuromi H, Briggs L, Green D, Rocha J, Sweeney S, et al. Bicaudal-D binds clathrin heavy chain to promote its transport and augments synaptic vesicle recycling. EMBO J. 2010;29:992-1006 pubmed publisher..Our results implicate BicD as a new player in clathrin-associated trafficking processes and show a novel requirement for microtubule-based motor transport in the synaptic vesicle cycle. ..
- Lin Y, Currinn H, Pocha S, Rothnie A, Wassmer T, Knust E. AP-2-complex-mediated endocytosis of Drosophila Crumbs regulates polarity by antagonizing Stardust. J Cell Sci. 2015;128:4538-49 pubmed publisher..This study provides evidence for a molecular mechanism, based on stabilization and endocytosis, to adjust surface levels of Crumbs, which are essential for maintaining epithelial polarity. ..
- Rogat A, Miller K. A role for myosin VI in actin dynamics at sites of membrane remodeling during Drosophila spermatogenesis. J Cell Sci. 2002;115:4855-65 pubmed..Regions of myosin VI accumulation are proposed as sites where actin assembly is coupled to membrane dynamics. ..
- Boehm M, Bonifacino J. Genetic analyses of adaptin function from yeast to mammals. Gene. 2002;286:175-86 pubmed..Here, we review recent progress in the genetic analysis of the function of AP complexes, focusing on studies that make use of targeted interference or naturally-occurring mutations in various model organisms. ..
- Stimson D, Estes P, Rao S, Krishnan K, Kelly L, Ramaswami M. Drosophila stoned proteins regulate the rate and fidelity of synaptic vesicle internalization. J Neurosci. 2001;21:3034-44 pubmed..on the presynaptic plasma membrane but do not alter the levels or distribution of endocytosis proteins, dynamin, alpha-adaptin, and clathrin. In addition, stn(8P1) mutants exhibit depletion and enlargement of synaptic vesicles...
- Lee D, Harris T. Coordinating the cytoskeleton and endocytosis for regulated plasma membrane growth in the early Drosophila embryo. Bioarchitecture. 2014;4:68-74 pubmed publisher..More generally, it provides a model for understanding how cytoskeletal-endocytic cross-talk regulates the assembly of a cell. ..
- Tang H, Rompani S, Atkins J, Zhou Y, Osterwalder T, Zhong W. Numb proteins specify asymmetric cell fates via an endocytosis- and proteasome-independent pathway. Mol Cell Biol. 2005;25:2899-909 pubmed..They contain distinct binding motifs for alpha-adaptin (alpha-Ada) and proteins with Eps15 homology (EH) domains, which regulate endocytosis, and for E3 ..
- Song Y, Lu B. Interaction of Notch signaling modulator Numb with ?-Adaptin regulates endocytosis of Notch pathway components and cell fate determination of neural stem cells. J Biol Chem. 2012;287:17716-28 pubmed publisher..Here we show that ?-Adaptin (?-Ada), a subunit of the endocytic AP-2 complex, interacts with Numb through a new mode of interaction to regulate NSC ..
- Orem N, Xia L, Dolph P. An essential role for endocytosis of rhodopsin through interaction of visual arrestin with the AP-2 adaptor. J Cell Sci. 2006;119:3141-8 pubmed
- Fang X, Zhou J, Liu W, Duan X, Gala U, Sandoval H, et al. Dynamin Regulates Autophagy by Modulating Lysosomal Function. J Genet Genomics. 2016;43:77-86 pubmed publisher..We also showed that other endocytic core machinery components like clathrin and AP2 play similar but not identical roles in regulating autophagy and lysosomal function as dynamin...
- Benhra N, Lallet S, Cotton M, Le Bras S, Dussert A, Le Borgne R. AP-1 controls the trafficking of Notch and Sanpodo toward E-cadherin junctions in sensory organ precursors. Curr Biol. 2011;21:87-95 pubmed publisher..Because AP-1 does not prevent endocytosis and recycling of the Notch ligand Delta, our data indicate that the DE-cadherin junctional domain may act as a launching pad through which endocytosed Notch ligand is trafficked for signaling. ..
- Raghu P, Coessens E, Manifava M, Georgiev P, Pettitt T, Wood E, et al. Rhabdomere biogenesis in Drosophila photoreceptors is acutely sensitive to phosphatidic acid levels. J Cell Biol. 2009;185:129-45 pubmed publisher..We propose that PA levels are critical for apical membrane transport events required for rhabdomere biogenesis. ..
- Estes P, Ho G, Narayanan R, Ramaswami M. Synaptic localization and restricted diffusion of a Drosophila neuronal synaptobrevin--green fluorescent protein chimera in vivo. J Neurogenet. 2000;13:233-55 pubmed..Utilities and implications of these studies are demonstrated or discussed. ..
- Rikhy R, Mavrakis M, Lippincott Schwartz J. Dynamin regulates metaphase furrow formation and plasma membrane compartmentalization in the syncytial Drosophila embryo. Biol Open. 2015;4:301-11 pubmed publisher..Based on these findings, we propose that cell cycle changes in dynamin orchestrate recruitment of actin regulatory machinery for PM furrow dynamics during the early mitotic cycles in the Drosophila embryo. ..
- Koh T, Korolchuk V, Wairkar Y, Jiao W, Evergren E, Pan H, et al. Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. J Cell Biol. 2007;178:309-22 pubmed..Based on these data, we hypothesize that Eps15 and Dap160 promote the efficiency of endocytosis from the plasma membrane by maintaining high concentrations of multiple endocytic proteins, including dynamin, at synapses. ..
- Richard D, Gilbert M, Crum B, Hollinshead D, Schelble S, Scheswohl D. Yolk protein endocytosis by oocytes in Drosophila melanogaster: immunofluorescent localization of clathrin, adaptin and the yolk protein receptor. J Insect Physiol. 2001;47:715-723 pubmed..melanogaster has been investigated by immunofluorescent localization of the endocytosis proteins, clathrin, alpha-adaptin and the putative yolk protein receptor (YP receptor)...
- Harris K, Zhang Y, Piccioli Z, Perrimon N, Littleton J. The postsynaptic t-SNARE Syntaxin 4 controls traffic of Neuroligin 1 and Synaptotagmin 4 to regulate retrograde signaling. elife. 2016;5: pubmed publisher..Our findings suggest a conserved postsynaptic SNARE machinery controls multiple aspects of retrograde signaling and cargo trafficking within the postsynaptic compartment. ..
- Rodrigues F, Shao W, Harris T. The Arf GAP Asap promotes Arf1 function at the Golgi for cleavage furrow biosynthesis in Drosophila. Mol Biol Cell. 2016;27:3143-3155 pubmed..We conclude that Asap is essential for Arf1 to function at the Golgi for cleavage furrow biosynthesis. Asap may recycle Arf1 to the Golgi from post-Golgi membranes, providing optimal Golgi output for specific stages of the cell cycle. ..
- Cherry S, Perrimon N. Entry is a rate-limiting step for viral infection in a Drosophila melanogaster model of pathogenesis. Nat Immunol. 2004;5:81-7 pubmed..Thus, this virus model provides a sensitive and efficient approach for identifying components required for pathogenesis. ..
- Jafar Nejad H, Norga K, Bellen H. Numb: "Adapting" notch for endocytosis. Dev Cell. 2002;3:155-6 pubmed..In this issue of Developmental Cell, Berdnik et al. show that Numb recruits alpha-Adaptin and that this physical interaction plays a role in downregulating Notch, presumably by stimulating ..
- Peng Y, Yang W, Lin W, Lai T, Chien C. Nak regulates Dlg basal localization in Drosophila salivary gland cells. Biochem Biophys Res Commun. 2009;382:108-13 pubmed publisher..The transition of Dlg distribution was disrupted in nak mutants. Nak associated with the AP-2 subunit alpha-Ada and the AP-1 subunit AP-1gamma...
- Cotton M, Benhra N, Le Borgne R. Numb inhibits the recycling of Sanpodo in Drosophila sensory organ precursor. Curr Biol. 2013;23:581-7 pubmed publisher..In numb mutant organs, Spdo is efficiently internalized and recycled back to the plasma membrane. We propose that Numb acts in concert with AP-1 to control the endocytic recycling of Spdo to regulate binary-fate decisions. ..
- Geisbrecht E, Montell D. Myosin VI is required for E-cadherin-mediated border cell migration. Nat Cell Biol. 2002;4:616-20 pubmed..Multiple biochemical mechanisms may exist, therefore, for cadherins to associate with diverse unconventional myosins that are required for normal stereocilium formation or maintenance. ..
- Ho Y, Lien M, Lin C, Wei S, Chang L, Hsu J. Echinoid regulates Flamingo endocytosis to control ommatidial rotation in the Drosophila eye. Development. 2010;137:745-54 pubmed publisher..Thus, co-endocytosis of Ed and Fmi provides a link between apicobasal polarity and PCP. ..
- 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..We first identified a human cDNA encoding delta-adaptin, a structural homolog of the alpha- and gamma-adaptin subunits of the clathrin coat adaptors AP-1 and AP-2, respectively...
- Gonzalez Gaitan M, Jackle H. The range of spalt-activating Dpp signalling is reduced in endocytosis-defective Drosophila wing discs. Mech Dev. 1999;87:143-51 pubmed
- Parkhurst S, Delidakis C. Fly developments: an introspective. Bioessays. 2003;25:87-9 pubmed
- Wirtz Peitz F, Nishimura T, Knoblich J. Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell. 2008;135:161-73 pubmed publisher..Our data reveal a molecular mechanism for the asymmetric localization of Numb and show how cell polarity can be coupled to cell-cycle progression. ..
- de Vreede G, Schoenfeld J, Windler S, Morrison H, Lu H, Bilder D. The Scribble module regulates retromer-dependent endocytic trafficking during epithelial polarization. Development. 2014;141:2796-802 pubmed publisher..We propose that the Scrib module regulates epithelial polarity by influencing endocytic itineraries of Crumbs and other retromer-dependent cargo. ..
- 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. ..
- Forjanic J, Chen C, Jackle H, Gonzalez Gaitan M. Genetic analysis of stomatogastric nervous system development in Drosophila using enhancer trap lines. Dev Biol. 1997;186:139-54 pubmed..Our results indicate that SNS development depends on pattern organizer genes including components of the Ras/Raf pathway. ..
- Robertson H, Hime G, Lada H, Bowtell D. A Drosophila analogue of v-Cbl is a dominant-negative oncoprotein in vivo. Oncogene. 2000;19:3299-308 pubmed
- Crosetto N, Tikkanen R, Dikic I. Oncogenic breakdowns in endocytic adaptor proteins. FEBS Lett. 2005;579:3231-8 pubmed..We discuss how breakdowns in the function of endocytic adaptors might facilitate impairment of tissue homeostasis and consequent tumor development. ..
- Chen X, Zhang B, Fischer J. A specific protein substrate for a deubiquitinating enzyme: Liquid facets is the substrate of Fat facets. Genes Dev. 2002;16:289-94 pubmed..The results show definitively that Lqf is the key substrate of Faf in the eye; Lqf concentration is Faf-dependent, Lqf is ubiquitinated in vivo and deubiquitinated by Faf, and Lqf and Faf interact physically. ..
- Kasprowicz J, Kuenen S, Swerts J, Miskiewicz K, Verstreken P. Dynamin photoinactivation blocks Clathrin and ?-adaptin recruitment and induces bulk membrane retrieval. J Cell Biol. 2014;204:1141-56 pubmed publisher..Hence, our data indicate that Dynamin is critically involved in the stabilization of Clathrin- and AP2-dependent endocytic pits.
- Xie X, Cho B, Fischer J. Drosophila Epsin's role in Notch ligand cells requires three Epsin protein functions: the lipid binding function of the ENTH domain, a single Ubiquitin interaction motif, and a subset of the C-terminal protein binding modules. Dev Biol. 2012;363:399-412 pubmed publisher..We propose that Epsin's specificity for Notch signaling simply reflects its unique ability to interact with the plasma membrane, Ubiquitin, and proteins that bind Clathrin. ..
- Prokop A, Uhler J, Roote J, Bate M. The kakapo mutation affects terminal arborization and central dendritic sprouting of Drosophila motorneurons. J Cell Biol. 1998;143:1283-94 pubmed..On the other, a specific type of sensory neuron (scolopidial neurons) shows defects in microtubule organization and detaches from its support cells. ..
- Rajan A, Tien A, Haueter C, Schulze K, Bellen H. The Arp2/3 complex and WASp are required for apical trafficking of Delta into microvilli during cell fate specification of sensory organ precursors. Nat Cell Biol. 2009;11:815-24 pubmed publisher..Our data indicate that WASp-dependent Arp2/3 actin polymerization is crucial for apical presentation of Delta, providing a mechanistic link between actin polymerization and Notch signalling...
- Gross G, Lone G, Leung L, Hartenstein V, Guo M. X11/Mint genes control polarized localization of axonal membrane proteins in vivo. J Neurosci. 2013;33:8575-86 pubmed publisher..Since X11/Mint binds to APP, and abnormal trafficking of APP contributes to Alzheimer's disease, deregulation of X11/Mint may be important for Alzheimer's disease pathogenesis. ..
- Vidal O, Stec W, Bausek N, Smythe E, Zeidler M. Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking. J Cell Sci. 2010;123:3457-66 pubmed publisher..As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade. ..
- Goldenberg G, Harris T. Adherens junction distribution mechanisms during cell-cell contact elongation in Drosophila. PLoS ONE. 2013;8:e79613 pubmed publisher..Overall, we propose that new synthesis, lateral diffusion, and endocytosis play overlapping roles to populate elongating cell-cell contacts with evenly distributed AJs in this in vivo system. ..
- Schweisguth F. Regulation of notch signaling activity. Curr Biol. 2004;14:R129-38 pubmed..Recent analyses of the cell biology of the Notch receptor have identified several fundamental mechanisms that contribute to regulate Notch signaling activity in space and time. ..