Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP
Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP
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DOI：
10.1111/j.1471-4159.2008.05335.x
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发表时间：
2008-05-01
影响因子：
4.7
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Nakazawa, Takanobu;Kuriu, Toshihiko;Yamamoto, Tadashi
NMDA 受体通过调节 Rho GTPases 来调节脊柱形态可塑性。然而，NMDA 受体介导的 Rho GTPases 调节的分子机制仍不清楚。在这项研究中，我们证明 p250GAP（一种 NMDA 受体相关 RhoGAP）通过调节 RhoA 活性来调节脊柱形态发生。 p250GAP 的敲除增加了脊柱宽度并提高了原代海马神经元中的内源性 RhoA 活性。 p250GAP 敲低导致的脊柱宽度增加被 RhoA 显性失活形式的表达所抑制。此外，p250GAP 参与 NMDA 受体介导的 RhoA 激活。为了响应 NMDA 受体激活，外源表达的绿色荧光蛋白 (GFP) 标记的 p250GAP 被重新分布。因此，这些数据表明 p250GAP 在 NMDA 受体介导的 RhoA 活性调节中发挥重要作用，从而导致脊柱形态可塑性。
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.