{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:02:41Z","timestamp":1792440161192,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["AI166293"],"award-info":[{"award-number":["AI166293"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["AI180416"],"award-info":[{"award-number":["AI180416"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["HL174593"],"award-info":[{"award-number":["HL174593"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["AI182645"],"award-info":[{"award-number":["AI182645"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["YAN23G0"],"award-info":[{"award-number":["YAN23G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:p>\n                    The adeno-associated virus receptor (AAVR; also known as KIAA0319L) is the proteinaceous receptor required for the transduction of multiserotype adeno-associated viruses (AAVs). While the extracellular polycystic kidney disease (PKD) domains of AAVR directly bind AAV capsids, the function of its C-terminal cytosolic domain (AAVR-C) in governing AAV internalization and intracellular trafficking remains undefined. Using targeted pulldown of AAVR-interacting host proteins with a glutathione S-Transferase (GST)-fused AAVR-C recombinant protein (GST-AAVR-C) as a bait, we identified that TBC1 domain family member 23 (TBC1D23), a specialized intracellular trafficking adaptor and bridging factor, binds AAVR via the AAVR-C and mediates AAV\u2019s endosome-to-\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -Golgi network (TGN) transport. Biolayer interferometry (BLI) demonstrates nanomolar-affinity binding between AAVR-C and the C-terminal scaffold domain of TBC1D23 (TBC1D23-C). CRISPR-mediated knockout of\n                    <jats:italic toggle=\"yes\">TBC1D23<\/jats:italic>\n                    severely impairs rAAV transduction across multiple human cell types, including polarized human airway epithelium (HAE). Loss of TBC1D23 disrupts convergence of internalized AAV capsids at the TGN, leading to diminished nuclear import of AAV vectors. Mutational analyses of AAVR-C reveal that its acidic residue cluster is required for TBC1D23 binding and AAV retrograde transport from the endosome to the TGN. Together, these findings define TBC1D23 as a receptor-proximal trafficking module that couples AAV\u2013AAVR engagement to vesicle transport, revealing a missing core regulatory step in AAV retrograde transport that is essential for productive rAAV transduction.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2605086123","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:24:01Z","timestamp":1786551841000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["TBC1D23\u2013AAVR interaction drives endosome-to-TGN trafficking required for rAAV transduction"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4268-4171","authenticated-orcid":false,"given":"Xiujuan","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3020-9990","authenticated-orcid":false,"given":"Ariful","family":"Habib","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1817-7915","authenticated-orcid":false,"given":"Shane","family":"McFarlin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-4810","authenticated-orcid":false,"given":"Donovan","family":"Richart","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Yeun","family":"Park","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham","place":["Birmingham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxi","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopedic Surgery and Sports Medicine, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8210-5567","authenticated-orcid":false,"given":"Ziying","family":"Yan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham","place":["Birmingham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9850-1695","authenticated-orcid":false,"given":"Jianming","family":"Qiu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.04.045"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.12.067"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02957-25"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.03.064"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.09.005"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00243-z"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16465"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00391-17"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2020.09.010"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00031-4"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3627"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2309910120"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl0608"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909316116"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-024-00763-z"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46166-2"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00163"},{"key":"e_1_3_4_19_2","first-page":"115","article-title":"An in vitro model of differentiated human airway epithelia. Methods for establishing primary cultures","volume":"188","author":"Karp P. H.","year":"2002","unstructured":"P. H. Karp , An in vitro model of differentiated human airway epithelia. Methods for establishing primary cultures. Methods Mol. Biol. 188, 115\u2013137 (2002).","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_4_20_2","first-page":"183","article-title":"Well-differentiated human airway epithelial cell cultures","volume":"107","author":"Fulcher M. L.","year":"2005","unstructured":"M. L. Fulcher , Well-differentiated human airway epithelial cell cultures. Methods Mol. Med. 107, 183\u2013206 (2005).","journal-title":"Methods Mol. Med."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604099200"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.6.2863-2874.2004"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.92"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2023.101115"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz139"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161800"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2180"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.024"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02520-14"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19840-4"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02919-4"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.10.2193"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1050"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.10.014"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.11.005"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.03.012"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.06.026"},{"key":"e_1_3_4_39_2","unstructured":"X. Zhang Data from \u201cInteracting proteins identified from a KIAA0319L C-terminus pulldown.\u201d MassIVE dataset. https:\/\/doi.org\/doi:10.25345\/C5WP9TM3B. Deposited 26 January 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2605086123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:24:13Z","timestamp":1786551853000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2605086123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":39,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2026,8,18]]}},"alternative-id":["10.1073\/pnas.2605086123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2605086123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"assertion":[{"value":"2026-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2605086123"}}