ノズミ　モトヒロ   野住　素広    所属   新潟薬科大学  医療技術学部 臨床検査学科    職種   教授
言語種別	英語
発行・発表の年月	2023/10/02
形態種別	論文 - 研究論文（学術雑誌）
査読	査読あり
標題	Very-long-chain fatty acids are crucial to neuronal polarity by providing sphingolipids to lipid rafts.
執筆形態	その他 - 指定なし
掲載誌名	Cell reports
掲載区分	国外
巻・号・頁	pp.113195-113195
著者・共著者	Atsuko Honda,Motohiro Nozumi,Yasuyuki Ito,Rie Natsume,Asami Kawasaki,Fubito Nakatsu,Manabu Abe,Haruki Uchino,Natsuki Matsushita,Kazutaka Ikeda,Makoto Arita,Kenji Sakimura,Michihiro Igarashi
概要	Fatty acids have long been considered essential to brain development; however, the involvement of their synthesis in nervous system formation is unclear. We generate mice with knockout of GPSN2, an enzyme for synthesis of very-long-chain fatty acids (VLCFAs) and investigate the effects. Both GPSN2-/- and GPSN2+/- mice show abnormal neuronal networks as a result of impaired neuronal polarity determination. Lipidomics of GPSN2-/- embryos reveal that ceramide synthesis is specifically inhibited depending on FA length; namely, VLCFA-containing ceramide is reduced. We demonstrate that lipid rafts are highly enriched in growth cones and that GPSN2+/- neurons lose gangliosides in their membranes. Application of C24:0 ceramide, but not C16:0 ceramide or C24:0 phosphatidylcholine, to GPSN2+/- neurons rescues both neuronal polarity determination and lipid-raft density in the growth cone. Taken together, our results indicate that VLCFA synthesis contributes to physiological neuronal development in brain network formation, in particular neuronal polarity determination through the formation of lipid rafts.
DOI	10.1016/j.celrep.2023.113195
PMID	37816355