p250GAP, a Novel Brain-enriched GTPase-activating.pdf

下载文档

8
0
约5.65万字
约 14页
2017-04-06 发布于江苏
举报
版权申诉
保障服务

p250GAP, a Novel Brain-enriched GTPase-activating.pdf

1、本文档共14页，可阅读全部内容。
2、有哪些信誉好的足球投注网站（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。

p250GAP, a Novel Brain-enriched GTPase-activating

Molecular Biology of the Cell Vol. 14, 2921–2934, July 2003 p250GAP, a Novel Brain-enriched GTPase-activating Protein for Rho Family GTPases, Is Involved in the N-Methyl-D-aspartate Receptor Signaling Takanobu Nakazawa,* Ayako M. Watabe,? Tohru Tezuka,* Yutaka Yoshida,* Kazumasa Yokoyama,* Hisashi Umemori,* Akihiro Inoue,? Shigeo Okabe,? Toshiya Manabe,?§ and Tadashi Yamamoto* *Division of Oncology, Department of Cancer Biology and ?Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo 108- 8639, Japan; ?Department of Anatomy and Cell Biology, School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan; and §Division of Cell Biology and Neurophysiology, Department of Neuroscience, Faculty of Medicine, Kobe University, Kobe 650-0017, Japan Submitted September 30, 2002; Revised March 9, 2003; Accepted March 9, 2003 Monitoring Editor: Tony Hunter N-Methyl-d-aspartate (NMDA) receptors regulate structural plasticity by modulating actin orga- nization within dendritic spines. Herein, we report identification and characterization of p250GAP, a novel GTPase-activating protein for Rho family proteins that interacts with the GluR2 (NR2B) subunit of NMDA receptors in vivo. The p250GAP mRNA was enriched in brain, with high expression in cortex, corpus striatum, hippocampus, and thalamus. Within neurons, p250GAP was highly concentrated in the postsynaptic density and colocalized with the GluR2 (NR2B) subunit of NMDA receptors and with postsynaptic density-95. p250GAP promoted GTP hydrolysis of Cdc42 and RhoA in vitro and in vivo. When overexpressed in neuroblastoma cells, p250GAP suppressed the activities of Rho family proteins, which resulted in alteration of neurite outgrowth. Finally, NMDA receptor stimulation led to dephosphorylation and redistribution of p250GAP in hippocampal slices. Together, p250GAP is likely to be involved in NMDA receptor activity-dependent actin reorganizatio