Distinct but overlapping functions for the closely related p190 RhoGAPs in neural development

Matheson, S. F., Hu, K. Q., Brouns, M. R., Sordella, R., VanderHeide, J. D., Settleman, J. (2006) Distinct but overlapping functions for the closely related p190 RhoGAPs in neural development. Developmental Neuroscience, 28 (6). pp. 538-50. ISSN 0378-5866 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17028431
DOI: 10.1159/000095116

Abstract

The p190 RhoGAPs, p190A and p190B, are highly related GTPase-activating proteins for the Rho GTPases. Rho GTPases and p190A reportedly control various aspects of brain development, and we hypothesized that p190B would be likewise involved in neuronal development. We find that like p190A, p190B is prominently expressed in the developing and adult brain. Unlike p190A, p190B is not abundantly tyrosine phosphorylated. We further demonstrate, using p190B-deficient mice, that p190B is required for normal brain development. Mice lacking p190B display several major defects, including (1) deficits in the formation of major forebrain commissures, including the corpus callosum and anterior commissure, (2) dilation of the lateral ventricles, suggesting inhibition of neurogenesis and/or survival, (3) thinning of the neocortical intermediate zone, suggesting defects in neuronal differentiation and/or axonal outgrowth, and (4) impaired neuronal differentiation. These defects are similar to, but distinct from, those described in p190A-deficient mice. RNA interference-mediated knockdown of neither p190 protein results in significant inhibition of neurite outgrowth in neuroblastoma cells, despite an apparent increase in RhoA activity. We conclude that p190 RhoGAPs control pivotal aspects of neural development, including neuronal differentiation and process outgrowth, and that these effects are mediated by signaling systems that include, but are not limited to, RhoA.

Item Type: Paper
Uncontrolled Keywords: Animals Brain abnormalities cytology metabolism Cell Differentiation physiology Cell Line Tumor DNA-Binding Proteins genetics metabolism Down-Regulation genetics GTPase Activating Proteins genetics metabolism Gene Expression Regulation Developmental physiology Growth Cones metabolism ultrastructure Mice Mice Knockout Nervous System Malformations genetics metabolism physiopathology Neurites metabolism ultrastructure Neurons/ cytology metabolism RNA Interference physiology Repressor Proteins genetics metabolism Signal Transduction physiology Stem Cells/cytology metabolism Telencephalon abnormalities cytology/metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
diseases & disorders > nervous system diseases and disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
organs, tissues, organelles, cell types and functions > organs types and functions > brain
CSHL Authors:
Communities: CSHL labs > Sordella lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 12 Dec 2011 19:04
Last Modified: 13 Mar 2013 16:03
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22861

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