A large percentage of current drugs target G-protein-coupled receptors, which couple to well-known signaling pathways involving cAMP or calcium. G-proteins themselves may subserve a second messenger function. Here, we review the role of tubulin and microtubules in directly mediating effects of heterotrimeric G-proteins on neuronal outgrowth, shape and differentiation. G-protein-tubulin interactions appear to be regulated by neurotransmitter activity, and, in turn, regulate the location of Gα in membrane microdomains (such as lipid rafts) or the cytosol. Tubulin binds with nanomolar affinity to Gsα, Giα1 and Gqα (but not other Gα subunits) as well as Gβ1γ2 subunits. Gα subunits destabilize microtubules by stimulating tubulin’s GTPase, while Gβγ subunits promote microtubule stability. The same region on Gsα that binds adenylyl cyclase and Gβγ also interacts with tubulin, suggesting that cytoskeletal proteins are novel Gα effectors. Additionally, intracellular Giα-GDP, in concert with other GTPase proteins and Gβγ, regulates the position of the mitotic spindle in mitosis. Thus, G-protein activation modulates cell growth and differentiation by directly altering microtubule stability. Further studies are needed to fully establish a structural mechanism of this interaction and its role in synaptic plasticity.
© 2009 S. Karger AG, Basel
- Lipid rafts
- Microtubule-associated protein
- Neurite outgrowth
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Mark M. Rasenick
Departments of Physiology and Biophysics, Psychiatry, and
Graduate Program in Neuroscience, University of Illinois
Chicago, IL 60612-7342 (USA)
Tel. +1 312 996 6641, Fax +1 312 996 1414, E-Mail email@example.com
Received: September 19, 2008
Accepted after revision: November 5, 2008
Published online: February 12, 2009
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 0, Number of References : 78
Vol. 17, No. 1, Year 2009 (Cover Date: February 2009)
Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)
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