p250GAP, a Novel Brain-enriched GTPase-activating Protein for Rho Family GTPases, Is Involved in the<i>N</i>-Methyl-<scp>d</scp>-aspartate Receptor Signaling

• Takanobu Nakazawa

  Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Ayako M. Watabe

  Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Tohru Tezuka

  Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Yutaka Yoshida

  Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Kazumasa Yokoyama

  Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Hisashi Umemori

  Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Akihiro Inoue

  Department of Anatomy and Cell Biology, School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan

• Shigeo Okabe

  Department of Anatomy and Cell Biology, School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan

• Toshiya Manabe

  Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

• Tadashi Yamamoto

  Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

抄録

N-Methyl-d-aspartate (NMDA) receptors regulate structural plasticity by modulating actin organization within dendritic spines. Herein, we report identification and characterization of p250GAP, a novel GTPase-activating protein for Rho family proteins that interacts with the GluRϵ2 (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 GluRϵ2 (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 reorganization in dendritic spines.

収録刊行物

• Molecular Biology of the Cell

  Molecular Biology of the Cell 14 (7), 2921-2934, 2003-07

  American Society for Cell Biology (ASCB)

キーワード

• Cell Biology
• Molecular Biology

詳細情報

• CRID: 1361981470932772096
• NII論文ID: 30018378550
• DOI: 10.1091/mbc.e02-09-0623
• ISSN: 19394586
• ISSN: 10591524
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