{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:12:23Z","timestamp":1779207143854,"version":"3.51.4"},"reference-count":79,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"the Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["22K06102,25K09613,A21H04770"],"award-info":[{"award-number":["22K06102,25K09613,A21H04770"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["22K06102"],"award-info":[{"award-number":["22K06102"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["25K09613"],"award-info":[{"award-number":["25K09613"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["A21H04770"],"award-info":[{"award-number":["A21H04770"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    VPS13A is an intracellular lipid transfer protein comprising more than 3,000 amino acids. Mutations in human VPS13A cause\n                    <jats:italic>VPS13A<\/jats:italic>\n                    disease, a neurodegenerative disorder that affects movement and cognition. VPS13A forms a complex with the membrane protein XK to mediate ATP-induced phospholipid scrambling in the plasma membrane. Here, we established a mouse cell system expressing full-length mouse VPS13A and examined its interaction with XK. Mutational analysis revealed that VPS13A binds to XK through a C-terminal \u03b2-strand that interacts with a \u03b2-hairpin in the central region of XK, an interaction essential for scramblase activity. The XK paralog XKR2, which contains a similar \u03b2-hairpin structure, also associates with VPS13A and supports phospholipid scrambling. We analyzed 10 mouse VPS13A variants corresponding to human patient mutations and classified them into 4 groups: (a) L67P, I90K, and W2453R, which showed reduced expression; (b) A1091P and M3080R, which were normally expressed but lacked scramblase activity; (c) S1446P, Q2689H, Y2713C, and R3084H, which modestly impaired expression or activity; and (d) I2763R, which altered cell size and disrupted ER independently of XK. These findings define the VPS13A\u2013XK interaction interface, clarify the functional impact of disease-causing mutations, and reveal an unexpected gain-of-function mutation of a VPS13A variant.\n                  <\/jats:p>\n                  <jats:p>In this study, we propose a model that explains how the neurodegenerative disease chorea-acanthocytosis develops.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1172\/jci200890","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:00:19Z","timestamp":1774368019000},"source":"Crossref","is-referenced-by-count":0,"title":["Four subtypes of disease-causing missense mutations underlie pathogenic protein interactions in neurodegenerative VPS13A disease"],"prefix":"10.1172","volume":"136","author":[{"given":"Xing","family":"Lin","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, The University of Osaka, Suita, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Ryoden","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, The University of Osaka, Suita, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chigure","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, The University of Osaka, Suita, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaharu","family":"Sakuragi","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, The University of Osaka, Suita, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Department of Cellular and Neuropathology, Graduate School of Medicine, Juntendo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9758-8426","authenticated-orcid":true,"given":"Shigekazu","family":"Nagata","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, The University of Osaka, Suita, Osaka, Japan."},{"name":"Center for Infectious Disease Education and Research, The University of Osaka, Suita, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1534061"},{"key":"B2"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26446"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062905"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/25152564231210339"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R117.000582"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.138"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12230"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R600021200"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.02.034"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00604-z"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252809"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.690727"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2015"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-024-01411-6"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51939-w"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature09583"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1236758"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-022-09842-w"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.020"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0037-0"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119286119"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000328"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260227"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205425119"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-08-0439-T"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"B28","doi-asserted-by":"crossref","unstructured":"Li D, et al. 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