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PMID: 10982854 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells.

Molecular and cellular biology ·Vol. 20 ·No. 19 ·2000-10-00 ·Pages 7378-87

Katoh H, Yasui H, Yamaguchi Y, Aoki J, Fujita H, Mori K, Negishi M

Abstract

The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes in various cell types. Among them, Rac and Cdc42 have been shown to be involved in neurite outgrowth in neuronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurite outgrowth in the absence of NGF, and the morphology of wild-type RhoG-expressing cells was similar to that of NGF-differentiated cells. Constitutively active RhoG-transfected cells extended short neurites but developed large lamellipodial or filopodial structures at the tips of neurites. RhoG-induced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition, expression of constitutively active RhoG elevated endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expression of dominant-negative RhoG suppressed the neurite outgrowth. Furthermore, constitutively active Ras-induced neurite outgrowth was also suppressed by dominant-negative RhoG. Taken together, these results suggest that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.

MeSH Terms
Animals Cell Differentiation/drug effects GTP Phosphohydrolases/biosynthesis,genetics,physiology Genes, Dominant Mutagenesis, Site-Directed Neoplasm Proteins/physiology Nerve Growth Factors/pharmacology Nerve Tissue Proteins/physiology Neurites/metabolism PC12 Cells/drug effects,metabolism,ultrastructure Rats Recombinant Fusion Proteins/physiology Signal Transduction Transfection cdc42 GTP-Binding Protein/physiology rac1 GTP-Binding Protein/physiology
Chemicals
Neoplasm Proteins Nerve Growth Factors Nerve Tissue Proteins Recombinant Fusion Proteins Rhog protein, rat GTP Phosphohydrolases cdc42 GTP-Binding Protein rac1 GTP-Binding Protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Katoh H
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Yasui H
Yamaguchi Y
Aoki J
Fujita H
Mori K
Negishi M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.19.7378-7387.2000
Published
2000-10-00
Pages
7378-87
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86291
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.19.7378-7387.2000 PMC Full Text View journal details
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