Regulation of spine morphology by RICS-dependent Cdc42 signaling

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Nakamura Tsutomu 東京大学, 定量生命科学研究所, 客員准教授 (30302798)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: シグナル伝達 / シナプス / スパイン / グルタミン酸受容体 / CaMKII / Cdc42 / アクチン

Outline of Final Research Achievements

We previously identified RICS, which is localized in the postsynaptic density and forms a complex with glutamate receptors and PSD-95. RICS functions as a Cdc42GAP that regulates the downstream Cdc42-mediated signaling. We hypothesized that RICS regulates the Cdc42-PAK-LIMK-Cofilin signaling pathway and tested the hypothesis in this study. We conducted in vitro experiments using primary cultured neurons derived from wild-type and RICS KO mice, inhibitors, and dominant negative mutants. We found that stimulation of neurons with glutamate leads to the activation of PAK, LIMK, and Cofilin in the CaMKII- or RICS-dependent manner. This finding suggests that glutamate, an excitatory neurotransmitter, activates Cdc42-PAK-LIMK-Cofilin signaling through glutamate receptors, CaMKII, and RICS.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

高次脳機能の重要な細胞基盤として、グルタミン酸の興奮性刺激に依存したスパイン形態やシナプス伝達効率の制御が考えられている。Cofilinはスパイン骨格を構成するアクチン線維の動態を調節するタンパク質なので、上記のシグナル伝達経路によるアクチン動態の調節が、スパイン形態やシナプス伝達効率の制御に関与している可能性が示唆された。