Channelpedia

PubMed 17438139


Referenced in: none

Automatically associated channels: Kir6.2



Title: Synaptic scaffolding molecule alpha is a scaffold to mediate N-methyl-D-aspartate receptor-dependent RhoA activation in dendrites.

Authors: 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

Journal, date & volume: Mol. Cell. Biol., 2007 Jun , 27, 4388-405

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17438139


Abstract
Synaptic scaffolding molecule (S-SCAM) interacts with a wide variety of molecules at excitatory and inhibitory synapses. It comprises three alternative splicing variants, S-SCAMalpha, -beta, and -gamma. We generated mutant mice lacking specifically S-SCAMalpha. S-SCAMalpha-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-SCAMalpha corrects this abnormal morphology, while S-SCAMbeta and -gamma 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-SCAMalpha. S-SCAMalpha fails to correct the abnormal spine morphology under the treatment of N-methyl-d-aspartate (NMDA) receptor inhibitor (AP-5), Ca(2+)/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-SCAMalpha, but not -beta, 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-SCAMalpha is a scaffold required to activate RhoA protein in response to NMDA receptor signaling in dendrites.