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PMID: 11672527 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway.

Cell ·Vol. 107 ·No. 2 ·2001-10-19 ·Pages 195-207

Billuart P, Winter CG, Maresh A, Zhao X, Luo L

Abstract

Mechanisms that regulate axon branch stability are largely unknown. Genome-wide analyses of Rho GTPase activating protein (RhoGAP) function in Drosophila using RNA interference identified p190 RhoGAP as essential for axon stability in mushroom body neurons, the olfactory learning and memory center. p190 inactivation leads to axon branch retraction, a phenotype mimicked by activation of GTPase RhoA and its effector kinase Drok and modulated by the level and phosphorylation of myosin regulatory light chain. Thus, there exists a retraction pathway from RhoA to myosin in maturing neurons, which is normally repressed by p190. Local regulation of p190 could control the structural plasticity of neurons. Indeed, genetic evidence supports negative regulation of p190 by integrin and Src, both implicated in neural plasticity.

MeSH Terms

Amino Acid Sequence Animals Axons/metabolism Cluster Analysis Cytoskeleton/metabolism DNA-Binding Proteins Drosophila GTPase-Activating Proteins Gene Deletion Genome Guanine Nucleotide Exchange Factors/physiology Immunohistochemistry Integrins/metabolism Learning Memory Mice Models, Biological Molecular Sequence Data Mutation Myosin Light Chains/metabolism Nuclear Proteins/physiology Phenotype Phosphorylation Protein Binding Protein Structure, Tertiary RNA, Bacterial/metabolism Rats Repressor Proteins Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Signal Transduction Transgenes rhoA GTP-Binding Protein/metabolism

Chemicals

Arhgap35 protein, mouse Arhgap35 protein, rat Arhgap5 protein, mouse DNA-Binding Proteins GTPase-Activating Proteins Guanine Nucleotide Exchange Factors Integrins Myosin Light Chains Nuclear Proteins RNA I RNA, Bacterial Repressor Proteins rhoA GTP-Binding Protein

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Billuart P

Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.

Winter C G

Maresh A

Zhao X

Luo L

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(01)00522-0

Published

2001-10-19

Pages

195-207

Language

English

Region

United States

NLM ID

0413066

Subset

Grants

NINDS NIH HHS · R01-NS 36632 · United States

Databases

GENBANK

AF387518

External Links

PubMed source DOI: 10.1016/s0092-8674(01)00522-0 View journal details

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Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway.

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