Hisako Nakayama    Department   School of Medicine, School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	A CDC42EP4/septin-based perisynaptic glial scaffold facilitates glutamate clearance.
Journal	Formal name：Nature Communications Abbreviation：Nat Commun ISSN code：20411723
Domestic / Foregin	Foregin
Volume, Issue, Page	6,pp.10090
Author and coauthor	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*
Publication date	2015/12
Summary	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