ハヤシ マリコ    Hayashi Mariko
   林 真理子
   所属
食健康科学部 管理栄養学科
 
生活機構研究科 生活科学研究専攻
 
女性健康科学研究所 所属教員
   職種
准教授
言語種別 英語
発行・発表の年月 2023/01
形態種別 学術雑誌
査読 査読あり
標題 Leucine 434 is essential for docosahexaenoic acid-induced augmentation of L-glutamate transporter current
執筆形態 共著
掲載誌名 J.Biol.Chem.
掲載区分国外
出版社・発行元 Elsevier
巻・号・頁 299(1),pp.102793
著者・共著者 ◎Kanako Takahashi Luying Chen, Misa Sayama, Mian Wu, Mariko Kato Hayashi, Tomohiko Irie, Tomohiko Ohwada, Kaoru Sato
概要 Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the forebrain to prevent excitotoxicity. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6 n-3) enhance synaptic transmission, and their target molecules include EAATs. Here, we aimed to investigate the effect of DHA on EAAT2 and identify the key amino acid for DHA/EAAT2 interaction by electrophysiological recording of L-Glu-induced current in Xenopus oocytes transfected with EAATs, their chimeras, and single mutants. DHA transiently increased the amplitude of EAAT2 but tended to decrease that of excitatory amino acid transporter subtype 1 (EAAT1), another astrocytic EAAT. Single mutation of leucine (Leu) 434 to alanine (Ala) completely suppressed the augmentation by DHA, while mutation of EAAT1 Ala 435 (corresponding to EAAT2 Leu434) to Leu changed the effect from suppression to augmentation. Other polyunsaturated fatty acids (docosapentaenoic acid, eicosapentaenoic acid, arachidonic acid, and α-linolenic acid) similarly augmented the EAAT2 current and suppressed the EAAT1 current. Finally, our docking analysis suggested the most stable docking site is the lipid crevice of EAAT2, in close proximity to the L-Glu and sodium binding sites, suggesting that the DHA/Leu434 interaction might affect the elevator-like slide and/or the shapes of the other binding sites. Collectively, our results highlight a key molecular detail in the DHA-induced regulation of synaptic transmission involving EAATs.
researchmap用URL https://www.sciencedirect.com/science/article/pii/S0021925822012364