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Cytosolic Gαs Acts as an Intracellular Messenger to Increase Microtubule Dynamics and Promote Neurite Outgrowth*S⃞

By Jiang-Zhou Yu, Rahul H. Dave, John A. Allen, Tulika Sarma and Mark M. Rasenick

Abstract

It is now evident that Gαs traffics into cytosol following G protein-coupled receptor activation, and α subunits of some heterotrimeric G-proteins, including Gαs bind to tubulin in vitro. Nevertheless, many features of G-protein-microtubule interaction and possible intracellular effects of G protein α subunits remain unclear. In this study, several biochemical approaches demonstrated that activated Gαs directly bound to tubulin and cellular microtubules, and fluorescence microscopy showed that cholera toxin-activated Gαs colocalized with microtubules. The activated, GTP-bound, Gαs mimicked tubulin in serving as a GTPase activator for β-tubulin. As a result, activated Gαs made microtubules more dynamic, both in vitro and in cells, decreasing the pool of insoluble microtubules without changing total cellular tubulin content. The amount of acetylated tubulin (an indicator of microtubule stability) was reduced in the presence of Gαs activated by mutation. Previous studies showed that cholera toxin and cAMP analogs may stimulate neurite outgrowth in PC12 cells. However, in this study, overexpression of a constitutively activated Gαs or activation of Gαs with cholera toxin in protein kinase A-deficient PC12 cells promoted neurite outgrowth in a cAMP-independent manner. Thus, it is suggested that activated Gαs acts as an intracellular messenger to regulate directly microtubule dynamics and promote neurite outgrowth. These data serve to link G-protein signaling with modulation of the cytoskeleton and cell morphology

Topics: Mechanisms of Signal Transduction
Publisher: American Society for Biochemistry and Molecular Biology
OAI identifier: oai:pubmedcentral.nih.gov:2667733
Provided by: PubMed Central
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