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Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP |
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| Authors: | Nakazawa Takanobu Kuriu Toshihiko Tezuka Tohru Umemori Hisashi Okabe Shigeo Yamamoto Tadashi |
| Institution: | Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan; Department of Neurophysiology, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, Sanuki, Kagawa, Japan; Molecular &Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan; Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan |
| Abstract: | 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. |
| Keywords: | dendritic spine NMDA receptor p250GAP RhoA spine morphogenesis |
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