Watabe-Uchida, M., John, K. A., Janas, J. A., Newey, S. E., Van Aelst, L.
(September 2006)
The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18.
Neuron, 51 (6).
pp. 727-39.
ISSN 0896-6273 (Print)
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
School of Biological Sciences > Publications |
| Depositing User: |
CSHL Librarian
|
| Date: |
21 September 2006 |
| Date Deposited: |
06 Dec 2011 20:03 |
| Last Modified: |
19 Sep 2014 18:52 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/22926 |
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