Synaptic scaffolding molecule α is a scaffold to mediate N-methyl-D-aspartate receptor-dependent RhoA activation in dendrites

Junko Iida, Hiroyoshi Ishizaki, Miki Okamoto-Tanaka, Akira Kawata, Kazutaka Sumita, Shintaro Ohgake, Yuji Sato, Hiroshi Yorifuji, Nobuyuki Nukina, Kazumasa Ohashi, Kensaku Mizuno, Tomonari Tsutsumi, Akira Mizoguchi, Jun Miyoshi, Yoshimi Takai, Yutaka Hata

研究成果: Article査読

35 被引用数 (Scopus)

抄録

Synaptic scaffolding molecule (S-SCAM) interacts with a wide variety of molecules at excitatory and inhibitory synapses. It comprises three alternative splicing variants, S-SCAMα, -β, and -γ. We generated mutant mice lacking specifically S-SCAMα. S-SCAMα-deficient mice breathe and feed normally but die within 24 h after birth. Primary cultured hippocampal neurons from mutant mice have abnormally elongated dendritic spines. Exogenously expressed S-SCAMα corrects this abnormal morphology, while S-SCAMβ and -γ have no effect. Active RhoA decreases in cortical neurons from mutant mice. Constitutively active RhoA and ROCKII shift the length of dendritic spines toward the normal level, whereas ROCK inhibitor (Y27632) blocks the effect by S-SCAMα. S-SCAMα fails to correct the abnormal spine morphology under the treatment of N-methyl-D-aspartate (NMDA) receptor inhibitor (AP-5), Ca2+/calmodulin kinase inhibitor (KN-62), or tyrosine kinase inhibitor (PP2). NMDA treatment increases active RhoA in dendrites in wild-type hippocampal neurons, but not in mutant neurons. The ectopic expression of S-SCAMα, but not -β, recovers the NMDA-responsive accumulation of active RhoA in dendrites. Phosphorylation of extracellular signal-regulated kinase 1/2 and Akt and calcium influx in response to NMDA are not impaired in mutant neurons. These data indicate that S-SCAMα is a scaffold required to activate RhoA protein in response to NMDA receptor signaling in dendrites.

本文言語English
ページ(範囲)4388-4405
ページ数18
ジャーナルMolecular and cellular biology
27
12
DOI
出版ステータスPublished - 2007 6

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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