ナカヤマ ヒサコ   Hisako Nakayama
  中山 寿子
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 A CDC42EP4/septin-based perisynaptic glial scaffold facilitates glutamate clearance.
掲載誌名 正式名:Nature Communications
略  称:Nat Commun
ISSNコード:20411723
掲載区分国外
巻・号・頁 6,10090頁
著者・共著者 AGETA-ISHIHARA Natsumi†, YAMAZAKI Maya, KONNO Kohtarou, NAKAYAMA Hisako, ABE Manabu, HASHIMOTO Kenji, NISHIOKA Tomoki, KAIBUCHI Kozo, HATTORI Satoko, MIYAKAWA Tsuyoshi, TANAKA Kohichi, HUDA Fathul, HIRAI Hirokazu, HASHIMOTO Kouichi, WATANABE Masahiko, SAKIMURA Kenji, KINOSHITA Makoto*
発行年月 2015/12
概要 The small GTPase-effector proteins CDC42EP1-5/BORG1-5 interact reciprocally with CDC42 or the septin cytoskeleton. Here we show that, in the cerebellum, CDC42EP4 is exclusively expressed in Bergmann glia and localizes beneath specific membrane domains enwrapping dendritic spines of Purkinje cells. CDC42EP4 forms complexes with septin hetero-oligomers, which interact with a subset of glutamate transporter GLAST/EAAT1. In Cdc42ep4(-/-) mice, GLAST is dissociated from septins and is delocalized away from the parallel fibre-Purkinje cell synapses. The excitatory postsynaptic current exhibits a protracted decay time constant, reduced sensitivity to a competitive inhibitor of the AMPA-type glutamate receptors (γDGG) and excessive baseline inward current in response to a subthreshold dose of a nonselective inhibitor of the glutamate transporters/EAAT1-5 (DL-TBOA). Insufficient glutamate-buffering/clearance capacity in these mice manifests as motor coordination/learning defects, which are aggravated with subthreshold DL-TBOA. We propose that the CDC42EP4/septin-based glial scaffold facilitates perisynaptic localization of GLAST and optimizes the efficiency of glutamate-buffering and clearance.
DOI 10.1038/ncomms10090
PMID 26657011