Cdc42 Facilitates Axonogenesis by Enhancing Microtubule Stabilization in Primary Hippocampal Neurons

The establishment of polarity is an essential process in early neuronal development. Cdc42, a GTPase of the Rho family, is a key regulator of cytoskeletal dynamics and neuronal polarity. However, the mechanisms underlying the action of cdc42 in regulating axonogenesis have not been elucidated. Here,...

Full description

Saved in:
Bibliographic Details
Published in:Cellular and molecular neurobiology 2021-10, Vol.41 (7), p.1599-1610
Main Authors: Li, Ang, Zhu, Hui-Ming, Chen, Yu, Yan, Fang, Liu, Zhong-Ying, Li, Zhen-Lin, Dong, Wei-Ren, Zhang, Lin, Wang, Hai-Hong
Format: Article
Language:English
Subjects:
Animals
Axonogenesis
Axons - metabolism
Axons - pathology
Biomedical and Life Sciences
Biomedicine
cdc42 GTP-Binding Protein - metabolism
Cdc42 protein
Cell Biology
Cell Polarity - physiology
Cells, Cultured
Collapsin response mediator protein 2
Cytoskeleton
Dendrites - metabolism
Dephosphorylation
Hippocampus
Hippocampus - metabolism
Mediator protein
Microtubules
Microtubules - metabolism
Mutants
Nerve Tissue Proteins - metabolism
Neurobiology
Neurogenesis - physiology
Neurons
Neurons - metabolism
Neurosciences
Original Research
Phosphorylation
Phosphorylation - physiology
Polarity
Rats
Rats, Sprague-Dawley
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The establishment of polarity is an essential process in early neuronal development. Cdc42, a GTPase of the Rho family, is a key regulator of cytoskeletal dynamics and neuronal polarity. However, the mechanisms underlying the action of cdc42 in regulating axonogenesis have not been elucidated. Here, we expressed wild-type cdc42, a constitutively active cdc42 mutant (cdc42F28L) and a dominant negative cdc42 mutant (cdc42N17), respectively, in the primary hippocampal neurons to alter the activity of cdc42. We found that cdc42 activities were paralleled with the capacities to promote axonogenesis in the cultured neurons. Cdc42 also enhanced microtubule stability in the cultured neurons. Pharmacologically stabilizing microtubules significantly abrogated the defective axonogenesis induced by cdc42 inhibition. Moreover, cdc42 promoted the dephosphorylation of collapsing response mediator protein-2 (CRMP-2) at Thr514 by increasing GSK-3β phosphorylation at Ser9 in the cultured neurons. These findings suggest that cdc42 may facilitate axonogenesis by promoting microtubule stabilization in rat primary hippocampal neurons.
ISSN:0272-4340
1573-6830
DOI:10.1007/s10571-021-01051-0