Activation of Rac1 Has an Opposing Effect on Induction and Maintenance of Long-Term Potentiation in Hippocampus by Acting on Different Kinases

Dongyang Cui; Xiaodong Jiang; Ming Chen; Huan Sheng; Da Shao; Li Yang; Xinli Guo; Yingqi Wang; Bin Lai; Ping Zheng

doi:10.3389/fnmol.2021.720371

Activation of Rac1 Has an Opposing Effect on Induction and Maintenance of Long-Term Potentiation in Hippocampus by Acting on Different Kinases

Front Mol Neurosci. 2021 Aug 31:14:720371. doi: 10.3389/fnmol.2021.720371. eCollection 2021.

Authors

Dongyang Cui¹, Xiaodong Jiang¹, Ming Chen¹, Huan Sheng¹, Da Shao¹, Li Yang¹, Xinli Guo¹, Yingqi Wang¹, Bin Lai¹, Ping Zheng^{1

2

3}

Affiliations

¹ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, School of Basic Medical Sciences, Fudan University, Shanghai, China.
² Department of Neurology of Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Pharmacology of Medical College of China Three Gorges University, Yichang, China.

Abstract

Rac1 is a small GTPase of the Rho family. A previous study showed that the activation of Rac1 had an opposing effect on induction and maintenance of long-term potentiation (LTP) in the hippocampus. However, the molecular mechanism underlying this opposing effect remains to be addressed. In the present work, we find that the activation of Rac1 during the induction of LTP leads to an activation of PKCι/λ by phosphatidylinositol-3-kinase (PI3K), whereas the activation of Rac1 during the maintenance of LTP leads to the inhibition of PKMζ by LIM_kinase (LIMK) in the hippocampus. This result suggests that during different stages of LTP, the activation of Rac1 can modulate different signaling pathways, which leads to an opposing effect on the induction and maintenance of LTP in the hippocampus.

Keywords: LIMK; PI3K; PKCι/λ; PKMζ; Rac1; long term potentiation.