The present address of Tohru Tezuka is the Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP
Article first published online: 10 MAR 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 105, Issue 4, pages 1384–1393, May 2008
How to Cite
Nakazawa, T., Kuriu, T., Tezuka, T., Umemori, H., Okabe, S. and Yamamoto, T. (2008), Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP. Journal of Neurochemistry, 105: 1384–1393. doi: 10.1111/j.1471-4159.2008.05335.x
- Issue published online: 10 MAR 2008
- Article first published online: 10 MAR 2008
- Received November 26, 2007; revised manuscript received February 22, 2008; accepted February 29, 2008.
- dendritic spine;
- NMDA receptor;
- spine morphogenesis
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.