The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18

Watabe-Uchida, M., John, K. A., Janas, J. A., Newey, S. E., Van Aelst, L. (2006) The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron, 51 (6). pp. 727-39. ISSN 0896-6273 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/16982419
DOI: 10.1016/j.neuron.2006.07.020

Abstract

The polarization of a neuron generally results in the formation of one axon and multiple dendrites, allowing for the establishment of neuronal circuitry. The molecular mechanisms involved in priming one neurite to become the axon, particularly those regulating the microtubule network, remain elusive. Here we report the identification of DOCK7, a member of the DOCK180-related protein superfamily, as a Rac GTPase activator that is asymmetrically distributed in unpolarized hippocampal neurons and selectively expressed in the axon. Knockdown of DOCK7 expression prevents axon formation, whereas overexpression induces formation of multiple axons. We further demonstrate that DOCK7 and Rac activation lead to phosphorylation and inactivation of the microtubule destabilizing protein stathmin/Op18 in the nascent axon and that this event is important for axon development. Our findings unveil a pathway linking the Rac activator DOCK7 to a microtubule regulatory protein and highlight the contribution of microtubule network regulation to axon development.

Item Type: Paper
Uncontrolled Keywords: Animals Axons metabolism Blotting Western Brain/growth development metabolism Cell Line Cell Line, Tumor Cell Polarity Cells, Cultured GTPase Activating Proteins/genetics/ metabolism Green Fluorescent Proteins geneticsmetabolism Hippocampus cytology metabolism Humans Microscopy Confocal Microscopy Fluorescence Neurons/cytology/ metabolism Phosphorylation Protein Binding Rats Recombinant Fusion Proteins genetics/metabolism Stathmin genetics/ metabolism Time Factors Transfection Two-Hybrid System Techniques rac GTP-Binding Proteins genetics/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Rac
organs, tissues, organelles, cell types and functions > tissues types and functions > axon
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells

organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > microtubule
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Van Aelst lab
Watson School > Publications
Depositing User: CSHL Librarian
Date Deposited: 06 Dec 2011 20:03
Last Modified: 19 Sep 2014 18:52
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22926

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