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

First Author  Watabe-Uchida M Year  2006
Journal  Neuron Volume  51
Issue  6 Pages  727-39
PubMed ID  16982419 Mgi Jnum  J:113648
Mgi Id  MGI:3687387 Doi  10.1016/j.neuron.2006.07.020
Citation  Watabe-Uchida M, et al. (2006) The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron 51(6):727-39
abstractText  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.
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