Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP.

Takanobu Nakazawa, Toshihiko Kuriu, Tohru Tezuka, Hisashi Umemori, Shigeo Okabe, Tadashi Yamamoto

Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.

Journal of neurochemistry 2008 May

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The NMDA receptor regulates spine morphological plasticity by modulating Rho GTPases. However, the molecular mechanisms for NMDA receptor-mediated regulation of Rho GTPases remain elusive. In this study, we show that p250GAP, an NMDA receptor-associated RhoGAP, regulates spine morphogenesis by modulating RhoA activity. Knock-down of p250GAP increased spine width and elevated the endogenous RhoA activity in primary hippocampal neurons. The increased spine width by p250GAP knock-down was suppressed by the expression of a dominant-negative form of RhoA. Furthermore, p250GAP is involved in NMDA receptor-mediated RhoA activation. In response to NMDA receptor activation, exogenously expressed green fluorescent protein (GFP)-tagged p250GAP was redistributed. Thus, these data suggest that p250GAP plays an important role in NMDA receptor-mediated regulation of RhoA activity leading to spine morphological plasticity.

Citation

Takanobu Nakazawa, Toshihiko Kuriu, Tohru Tezuka, Hisashi Umemori, Shigeo Okabe, Tadashi Yamamoto. Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP. Journal of neurochemistry. 2008 May;105(4):1384-93