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dc.contributor.authorNakato, Mitsuhiroen
dc.contributor.authorShiranaga, Naokoen
dc.contributor.authorTomioka, Maikoen
dc.contributor.authorWatanabe, Hitomien
dc.contributor.authorKurisu, Junkoen
dc.contributor.authorKengaku, Minekoen
dc.contributor.authorKomura, Naokoen
dc.contributor.authorAndo, Hiromuneen
dc.contributor.authorKimura, Yasuhisaen
dc.contributor.authorKioka, Noriyukien
dc.contributor.authorUeda, Kazumitsuen
dc.contributor.alternative中塔, 充宏ja
dc.contributor.alternative白永, 直子ja
dc.contributor.alternative冨岡, 麻衣子ja
dc.contributor.alternative渡邊, 仁美ja
dc.contributor.alternative栗栖, 純子ja
dc.contributor.alternative見学, 美根子ja
dc.contributor.alternative河村, 奈緒子ja
dc.contributor.alternative安藤, 弘宗ja
dc.contributor.alternative木村, 泰久ja
dc.contributor.alternative木岡, 紀幸ja
dc.contributor.alternative植田, 和光ja
dc.date.accessioned2021-12-17T08:32:06Z-
dc.date.available2021-12-17T08:32:06Z-
dc.date.issued2021-
dc.identifier.urihttp://hdl.handle.net/2433/266615-
dc.descriptionLarge transporter protein linked to schizophrenia. 京都大学プレスリリース. 2021-01-07.en
dc.descriptionABCA13の異常によるコレステロール輸送障害が統合失調症を引き起こすことを解明. 京都大学プレスリリース. 2021-01-08.ja
dc.description.abstractATP-binding cassette subfamily A member 13 (ABCA13) is predicted to be the largest ABC protein, consisting of 5, 058 amino acids and a long N-terminal region. Mutations in the ABCA13 gene were reported to increase the susceptibility to schizophrenia, bipolar disorder and major depression. However, little is known about the molecular functions of ABCA13 or how they associate with psychiatric disorders. Here, we examined the biochemical activity of ABCA13 using HEK293 cells transfected with mouse ABCA13. The expression of ABCA13 induced the internalization of cholesterol and gangliosides from the plasma membrane to intracellular vesicles. Cholesterol internalization by ABCA13 required the long N-terminal region and ATP hydrolysis. To examine the physiological roles of ABCA13, we generated Abca13 KO mice using CRISPR/Cas and found that these mice exhibited deficits of prepulse inhibition. Vesicular cholesterol accumulation and synaptic vesicle endocytosis were impaired in primary cultures of Abca13 KO cortical neurons. Furthermore, mutations in ABCA13 gene associated with psychiatric disorders disrupted the protein’s subcellular localization and impaired cholesterol trafficking. These findings suggest that ABCA13 accelerates cholesterol internalization by endocytic retrograde transport in neurons and that loss-of-this function is associated with the pathophysiology of psychiatric disorders.en
dc.language.isoeng-
dc.publisherElsevier BVen
dc.rights© 2020 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.en
dc.rightsThis is an open access article under the Creative Commons Attribution 4.0 International license.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/-
dc.subjectABC proteinsen
dc.subjectATP binding cassette subfamily A member 13 (ABCA13)en
dc.subjectpsychiatric disordersen
dc.subjectcholesterolen
dc.subjectgangliosidesen
dc.subjectprepulse inhibitionen
dc.subjectendocytic retrograde transporten
dc.subjectsynaptic vesicle endocytosisen
dc.titleABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol traffickingen
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleJournal of Biological Chemistryen
dc.identifier.volume296-
dc.relation.doi10.1074/jbc.RA120.015997-
dc.textversionpublisher-
dc.identifier.artnum100166-
dc.identifier.pmid33293368-
dc.relation.urlhttps://www.kyoto-u.ac.jp/en/research-news/2021-01-07-1-
dc.relation.urlhttps://www.kyoto-u.ac.jp/ja/research-news/2021-01-08-2-
dcterms.accessRightsopen access-
datacite.awardNumber18H05269-
datacite.awardNumber.urihttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18H05269/-
dc.identifier.pissn0021-9258-
dc.identifier.eissn1083-351X-
jpcoar.funderName日本学術振興会ja
jpcoar.awardTitle脂質輸送型ABC蛋白質の謎に迫るja
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