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タイトル: | ABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol trafficking |
著者: | Nakato, Mitsuhiro Shiranaga, Naoko Tomioka, Maiko Watanabe, Hitomi ![]() ![]() Kurisu, Junko Kengaku, Mineko ![]() ![]() ![]() Komura, Naoko Ando, Hiromune Kimura, Yasuhisa Kioka, Noriyuki ![]() ![]() ![]() Ueda, Kazumitsu ![]() ![]() ![]() |
著者名の別形: | 中塔, 充宏 白永, 直子 冨岡, 麻衣子 渡邊, 仁美 栗栖, 純子 見学, 美根子 河村, 奈緒子 安藤, 弘宗 木村, 泰久 木岡, 紀幸 植田, 和光 |
キーワード: | ABC proteins ATP binding cassette subfamily A member 13 (ABCA13) psychiatric disorders cholesterol gangliosides prepulse inhibition endocytic retrograde transport synaptic vesicle endocytosis |
発行日: | 2021 |
出版者: | Elsevier BV |
誌名: | Journal of Biological Chemistry |
巻: | 296 |
論文番号: | 100166 |
抄録: | ATP-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. |
記述: | Large transporter protein linked to schizophrenia. 京都大学プレスリリース. 2021-01-07. ABCA13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. |
著作権等: | © 2020 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the Creative Commons Attribution 4.0 International license. |
URI: | http://hdl.handle.net/2433/266615 |
DOI(出版社版): | 10.1074/jbc.RA120.015997 |
PubMed ID: | 33293368 |
関連リンク: | https://www.kyoto-u.ac.jp/en/research-news/2021-01-07-1 https://www.kyoto-u.ac.jp/ja/research-news/2021-01-08-2 |
出現コレクション: | 学術雑誌掲載論文等 |
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