Cdc42 Promotes Axonogenesis of Primary Hippocampal Neurons by Inhibiting Glycogen Synthase Kinase-3β.

Progressive axon degeneration is a common pathological feature of neurodegenerative diseases. Cdc42 is a member of the Rho GTPase family that participates in axonogenesis. GSK-3β is a serine/threonine kinase highly implicated in neuronal development and neurodegeneration. This study aimed to examine whether cdc42 promotes axonogenesis by regulating GSK-3β activity. Hippocampal neurons were isolated from neonatal Sprague-Dawley rats and transfected with designated plasmid vectors to alter the activities of cdc42 and GSK-3β. LiCl treatment was used to inhibit the GSK-3β activity in primary neurons. GSK-3β activity was determined by an enzyme activity assay kit. Immunofluorescence staining was used to detect axons stained with anti-Tau-1 antibody and dendrites stained with anti-MAP2 antibody. Transfection with an active cdc42 mutant (cdc42F28L) decreased the activity of GSK-3β and induced axonogenesis in primary rat hippocampal neurons, while transfection with a negative cdc42 mutant (cdc42N17) resulted an opposite effect. Moreover, transfection with plasmid vectors carrying wild-type GSK-3β or a constitutively active GSK3β mutant (GSK-3β S9A) increased the activity of GSK-3β and attenuated axonogenesis of primary hippocampal neurons with excessive cdc42 activity, whereas inhibition of GSK-3β by LiCl abolished the inhibitory effect of the negative cdc42 mutant on axonogenesis. This study suggests that cdc42 induces axonogenesis of primary rat hippocampal neurons via inhibiting GSK-3β activity. These findings support further investigation into the mechanisms of cdc42/GSK-3β-mediated axonogenesis. © 2022 The Author(s). Published by IMR Press.

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Yu-Ting Li, Fang-Zheng Chen, Wei Chen, Hui-Ming Zhu, Yu Chen, Zhen-Lin Li, Fang Yan, Zhong-Ying Liu, Wei-Ren Dong, Lin Zhang, Hai-Hong Wang. Cdc42 Promotes Axonogenesis of Primary Hippocampal Neurons by Inhibiting Glycogen Synthase Kinase-3β. Journal of integrative neuroscience. 2022 Jul 22;21(5):133

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PMID: 36137969

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