{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T15:34:14Z","timestamp":1769096054061,"version":"3.49.0"},"reference-count":31,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:p> Recently, genetic studies have implicated KIAA0319 in developmental dyslexia, the most common of the childhood learning disorders. The first functional data indicated that the KIAA0319 protein is expressed on the plasma membrane and may be involved in neuronal migration. Further analysis of the subcellular distribution of the overexpressed protein in mammalian cells indicates that KIAA0319 can colocalize with the early endosomal marker early endosome antigen 1 (EEA1) in large intracellular vesicles, suggesting that it is endocytosed. Antibody internalization assays with full-length KIAA0319 and deletion constructs confirmed that KIAA0319 is internalized and showed the importance of the cytoplasmic juxtamembranal region in this process. The present study has identified the medium subunit (\u03bc2) of adaptor protein 2 (AP-2) as a binding partner of KIAA0319 in a yeast two-hybrid screen. Using Rab5 mutants or depletion of the \u03bc-subunit of AP-2 or clathrin heavy chain by RNA interference, we demonstrate that KIAA0319 follows a clathrin-mediated endocytic pathway. We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. These results suggest the surface expression of KIAA0319 is regulated by endocytosis, supporting the idea that the internalization and recycling of the protein may be involved in fine tuning its role in neuronal migration. <\/jats:p>","DOI":"10.1152\/ajpcell.00630.2008","type":"journal-article","created":{"date-parts":[[2009,5,7]],"date-time":"2009-05-07T00:54:49Z","timestamp":1241657689000},"page":"C160-C168","source":"Crossref","is-referenced-by-count":33,"title":["The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway"],"prefix":"10.1152","volume":"297","author":[{"given":"Clotilde","family":"Levecque","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Velayos-Baeza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe G.","family":"Holloway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony P.","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Aguilar RC, Ohno H, Roche KW, Bonifacino JS. Functional domain mapping of the clathrin-associated adaptor medium chains mu1 and mu2. J Biol Chem 272: 27160\u201327166, 1997.","DOI":"10.1074\/jbc.272.43.27160"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Anthoni H, Zucchelli M, Matsson H, Muller-Myhsok B, Fransson I, Schumacher J, Massinen S, Onkamo P, Warnke A, Griesemann H, Hoffmann P, Nopola-Hemmi J, Lyytinen H, Schulte-Korne G, Kere J, Nothen MM, and Peyrard-Janvid M. A locus on 2p12 containing the co-regulated MRPL19 and C2ORF3 genes is associated to dyslexia. Hum Mol Genet 16: 667\u2013677, 2007.","DOI":"10.1093\/hmg\/ddm009"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Benmerah A, Lamaze C. Clathrin-coated pits: vive la difference? Traffic 8: 970\u2013982, 2007.","DOI":"10.1111\/j.1600-0854.2007.00585.x"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Bonifacino JS, Dell'Angelica EC. Molecular bases for the recognition of tyrosine-based sorting signals. J Cell Biol 145: 923\u2013926, 1999.","DOI":"10.1083\/jcb.145.5.923"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Bonifacino JS, Traub LM. Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 72: 395\u2013447, 2003.","DOI":"10.1146\/annurev.biochem.72.121801.161800"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Bryant DM, Stow JL. The ins and outs of E-cadherin trafficking. Trends Cell Biol 14: 427\u2013434, 2004.","DOI":"10.1016\/j.tcb.2004.07.007"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Bucci C, Parton RG, Mather IH, Stunnenberg H, Simons K, Hoflack B, Zerial M. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70: 715\u2013728, 1992.","DOI":"10.1016\/0092-8674(92)90306-W"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Cavalli V, Corti M, Gruenberg J. Endocytosis and signaling cascades: a close encounter. FEBS Lett 498: 190\u2013196, 2001.","DOI":"10.1016\/S0014-5793(01)02484-X"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 422: 37\u201344, 2003.","DOI":"10.1038\/nature01451"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Fisher SE, Francks C. Genes, cognition and dyslexia: learning to read the genome. Trends Cogn Sci 10: 250\u2013257, 2006.","DOI":"10.1016\/j.tics.2006.04.003"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Francks C, Paracchini S, Smith SD, Richardson AJ, Scerri TS, Cardon LR, Marlow AJ, MacPhie IL, Walter J, Pennington BF, Fisher SE, Olson RK, DeFries JC, Stein JF, Monaco AP. A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States. Am J Hum Genet 75: 1046\u20131058, 2004.","DOI":"10.1086\/426404"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Fromont-Racine M, Rain JC, Legrain P. Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens. Nat Genet 16: 277\u2013282, 1997.","DOI":"10.1038\/ng0797-277"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Galaburda AM, LoTurco J, Ramus F, Fitch RH, Rosen GD. From genes to behavior in developmental dyslexia. Nat Neurosci 9: 1213\u20131217, 2006.","DOI":"10.1038\/nn1772"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Gong Q, Huntsman C, Ma D. Clathrin-independent internalization and recycling. J Cell Mol Med 12: 126\u2013144, 2008.","DOI":"10.1111\/j.1582-4934.2007.00148.x"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"McGrath LM, Smith SD, Pennington BF. Breakthroughs in the search for dyslexia candidate genes. Trends Mol Med 12: 333\u2013341, 2006.","DOI":"10.1016\/j.molmed.2006.05.007"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"McLauchlan H, Newell J, Morrice N, Osborne A, West M, Smythe E. A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits. Curr Biol 8: 34\u201345, 1998.","DOI":"10.1016\/S0960-9822(98)70018-1"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Nakatsu F, Ohno H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct 28: 419\u2013429, 2003.","DOI":"10.1247\/csf.28.419"},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Paracchini S, Scerri T, Monaco AP. The genetic lexicon of dyslexia. Annu Rev Genomics Hum Genet 8: 57\u201379, 2007.","DOI":"10.1146\/annurev.genom.8.080706.092312"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Paracchini S, Thomas A, Castro S, Lai C, Paramasivam M, Wang Y, Keating BJ, Taylor JM, Hacking DF, Scerri T, Francks C, Richardson AJ, Wade-Martins R, Stein JF, Knight JC, Copp AJ, Loturco J, Monaco AP. The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum Mol Genet 15: 1659\u20131666, 2006.","DOI":"10.1093\/hmg\/ddl089"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Robinson MS. Adaptable adaptors for coated vesicles. Trends Cell Biol 14: 167\u2013174, 2004.","DOI":"10.1016\/j.tcb.2004.02.002"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"Rosenfeld JL, Moore RH, Zimmer KP, Alpizar-Foster E, Dai W, Zarka MN, Knoll BJ. Lysosome proteins are redistributed during expression of a GTP-hydrolysis-defective rab5a. J Cell Sci 114: 4499\u20134508, 2001.","DOI":"10.1242\/jcs.114.24.4499"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Somsel Rodman J and Wandinger-Ness A. Rab GTPases coordinate endocytosis. J Cell Sci 113: 183\u2013192, 2000.","DOI":"10.1242\/jcs.113.2.183"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Stein MP, Dong J and Wandinger-Ness A. Rab proteins and endocytic trafficking: potential targets for therapeutic intervention. Adv Drug Deliv Rev 55: 1421\u20131437, 2003.","DOI":"10.1016\/j.addr.2003.07.009"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"Stenmark H, Parton RG, Steele-Mortimer O, Lutcke A, Gruenberg J, Zerial M. Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J 13: 1287\u20131296, 1994.","DOI":"10.1002\/j.1460-2075.1994.tb06381.x"},{"key":"R25","doi-asserted-by":"crossref","unstructured":"Traub LM. Common principles in clathrin-mediated sorting at the Golgi and the plasma membrane. Biochim Biophys Acta 1744: 415\u2013437, 2005.","DOI":"10.1016\/j.bbamcr.2005.04.005"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Velayos-Baeza A, Toma C, da Roza S, Paracchini S, Monaco AP. Alternative splicing in the dyslexia-associated gene KIAA0319. Mamm Genome 18: 627\u2013634, 2007.","DOI":"10.1007\/s00335-007-9051-3"},{"key":"R27","doi-asserted-by":"crossref","unstructured":"Velayos-Baeza A, Toma C, Paracchini S, Monaco AP. The dyslexia-associated gene KIAA0319 encodes highly N- and O-glycosylated plasma membrane and secreted isoforms. Hum Mol Genet 17: 859\u2013871, 2008.","DOI":"10.1093\/hmg\/ddm358"},{"key":"R28","doi-asserted-by":"crossref","unstructured":"Williams J, O'Donovan MC. The genetics of developmental dyslexia. Eur J Hum Genet 14: 681\u2013689, 2006.","DOI":"10.1038\/sj.ejhg.5201575"},{"key":"R29","doi-asserted-by":"crossref","unstructured":"Wolfe BL, Trejo J. Clathrin-dependent mechanisms of G protein-coupled receptor endocytosis. Traffic 8: 462\u2013470, 2007.","DOI":"10.1111\/j.1600-0854.2007.00551.x"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Yap AS, Crampton MS, Hardin J. Making and breaking contacts: the cellular biology of cadherin regulation. Curr Opin Cell Biol 19: 508\u2013514, 2007.","DOI":"10.1016\/j.ceb.2007.09.008"},{"key":"R31","doi-asserted-by":"crossref","unstructured":"Zerial M, McBride H. Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2: 107\u2013117, 2001.","DOI":"10.1038\/35052055"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00630.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:18:29Z","timestamp":1718644709000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00630.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1152\/ajpcell.00630.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00630.2008","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7]]}}}