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Cited by 208Axon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanismsProtein Kinase Regulation and GTPase Signaling

The Rac Activator DOCK7 Regulates Neuronal Polarity through Local Phosphorylation of Stathmin/Op18

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Watabe-Uchida, Mitsuko, John, Keisha A., Janas, Justyna A., Newey, Sarah E., Van Aelst, Linda·2006·Neuron
DOI 10.1016/j.neuron.2006.07.020
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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.

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References 65 · Cited by 208

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Authors
Watabe-Uchida, M., John, K. A., Janas, J. A., Newey, S. E., & Van Aelst, L.
Affiliations
Cold Spring Harbor Laboratory (US)
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2006-09
Volume
51
Issue
6
Pages
727-739
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2006.07.020
OpenAlex
W1970574518
Cited by
208
References
65
Citations by year
2026: 4 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 15 · 2013: 19 · 2012: 18
FWCI
7.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
DOCK7, neuronal polarity, axon development, microtubule destabilization, hippocampal neurons, asymmetric protein distribution, axon formation, neurite outgrowth
MeSH terms
Animals, Axons, Brain, Cell Line, Cells, Cultured, Hippocampus, Humans, Microscopy, Fluorescence, Neurons, Phosphorylation, Protein Binding, Recombinant Fusion Proteins, Time Factors, Transfection, Blotting, Western, Cell Polarity, Microscopy, Confocal, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, rac GTP-Binding Proteins, Two-Hybrid System Techniques, Cell Line, Tumor, Green Fluorescent Proteins, Stathmin, Rats

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