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Cytosolic G{alpha}s acts as an intracellular messenger to increase microtubule dynamics and promote neurite outgrowth.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2009 Apr 17; Vol. 284 (16), pp. 10462-72. Date of Electronic Publication: 2009 Feb 19. - Publication Year :
- 2009
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Abstract
- It is now evident that Galpha(s) traffics into cytosol following G protein-coupled receptor activation, and alpha subunits of some heterotrimeric G-proteins, including Galpha(s) bind to tubulin in vitro. Nevertheless, many features of G-protein-microtubule interaction and possible intracellular effects of G protein alpha subunits remain unclear. In this study, several biochemical approaches demonstrated that activated Galpha(s) directly bound to tubulin and cellular microtubules, and fluorescence microscopy showed that cholera toxin-activated Galpha(s) colocalized with microtubules. The activated, GTP-bound, Galpha(s) mimicked tubulin in serving as a GTPase activator for beta-tubulin. As a result, activated Galpha(s) 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 Galpha(s) 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 Galpha(s) or activation of Galpha(s) with cholera toxin in protein kinase A-deficient PC12 cells promoted neurite outgrowth in a cAMP-independent manner. Thus, it is suggested that activated Galpha(s) 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.
- Subjects :
- Animals
Cholera Toxin metabolism
Cyclic AMP analogs & derivatives
Cyclic AMP metabolism
Cyclic AMP-Dependent Protein Kinases genetics
Cyclic AMP-Dependent Protein Kinases metabolism
GTP-Binding Protein alpha Subunits genetics
Guanosine Triphosphate metabolism
Neurites ultrastructure
PC12 Cells
Protein Isoforms genetics
Rats
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Second Messenger Systems physiology
Tubulin metabolism
Cytosol metabolism
GTP-Binding Protein alpha Subunits metabolism
Microtubules metabolism
Neurites metabolism
Protein Isoforms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 284
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19237344
- Full Text :
- https://doi.org/10.1074/jbc.M809166200