Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP.
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.
Nakazawa
Takanobu
T
Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Kuriu
Toshihiko
T
Tezuka
Tohru
T
Umemori
Hisashi
H
Okabe
Shigeo
S
Yamamoto
Tadashi
T
D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C085379:rho GTPase-activating protein