Rho–Rho-Kinase Regulates Ras-ERK Signaling Through SynGAP1 for Dendritic Spine Morphology

Mengya Wu, Yasuhiro Funahashi, Tetsuya Takano, Emran Hossen, Rijwan Uddin Ahammad, Daisuke Tsuboi, Mutsuki Amano, Kiyofumi Yamada, Kozo Kaibuchi

研究成果: ジャーナルへの寄稿学術論文査読

6 被引用数 (Scopus)


The structural plasticity of dendritic spines plays a critical role in NMDA-induced long-term potentiation (LTP) in the brain. The small GTPases RhoA and Ras are considered key regulators of spine morphology and enlargement. However, the regulatory interaction between RhoA and Ras underlying NMDA-induced spine enlargement is largely unknown. In this study, we found that Rho-kinase/ROCK, an effector of RhoA, phosphorylated SynGAP1 (a synaptic Ras-GTPase activating protein) at Ser842 and increased its interaction with 14-3-3ζ, thereby activating Ras-ERK signaling in a reconstitution system in HeLa cells. We also found that the stimulation of NMDA receptor by glycine treatment for LTP induction stimulated SynGAP1 phosphorylation, Ras-ERK activation, spine enlargement and SynGAP1 delocalization from the spines in striatal neurons, and these effects were prevented by Rho-kinase inhibition. Rho-kinase-mediated phosphorylation of SynGAP1 appeared to increase its dissociation from PSD95, a postsynaptic scaffolding protein located at postsynaptic density, by forming a complex with 14-3-3ζ. These results suggest that Rho-kinase phosphorylates SynGAP1 at Ser842, thereby activating the Ras-ERK pathway for NMDA-induced morphological changes in dendritic spines.

ジャーナルNeurochemical Research
出版ステータス出版済み - 09-2022

All Science Journal Classification (ASJC) codes

  • 生化学
  • 細胞および分子神経科学


「Rho–Rho-Kinase Regulates Ras-ERK Signaling Through SynGAP1 for Dendritic Spine Morphology」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。