The relationship of G(o)alpha subunit deamidation to the tissue distribution, nucleotide binding properties, and betagamma dimer interactions of G(o)alpha subunit isoforms.
The distribution and properties in brain of the alpha subunits of the major bovine brain Go isoforms, GoA, GoB and GoC, were characterized. The alpha(o)A and alpha(o)B isoforms arise from alternative splicing of RNAs from a single alpha(o) gene, whereas alpha(o)C is a deamidated form of alpha(o)A. All three Go isoforms purify from brain with different populations of betagamma dimers. This variable subunit composition of Go heterotrimers is likely a consequence of their functional differences. This study examined the biochemical properties of the alpha(o) isoforms to see if these properties explain the variable betagamma composition of their heterotrimers. The brain distribution of alpha(o)B differed substantially from that of alpha(o)A and alpha(o)C, as did its guanine nucleotide binding properties. The unique subunit composition of GoB can be explained by its expression in different brain regions. The alpha(o)A and alpha(o)C showed slight differences in guanine nucleotide binding properties but no preference for particular betagamma dimers when reassociated with a heterogeneous betagamma pool. The alpha(o)C protein occurred in a constant ratio to alpha(o)A throughout the brain, but was a much larger percent of total brain alpha(o) than previously thought, approximately 35%. These results suggest that alpha(o)A is a precursor of alpha(o)C and that the association of G(o)alpha subunits with different betagamma dimers reflects the function of an adaptive, G-protein signaling mechanism in brain.
McIntire
W E
WE
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Dingus
J
J
Wilcox
M D
MD
Hildebrandt
J D
JD
D000818:Animals; D000906:Antibodies; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D019281:Dimerization; D004492:Edetic Acid / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000494:pharmacology; D015151:Immunoblotting; D007536:Isomerism; D015636:Magnesium Chloride / Q000494:pharmacology; D008568:Memory / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D002614:Chelating Agents; D015636:Magnesium Chloride; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004492:Edetic Acid; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go