Signaling through Gz
Several studies have been carried out to pinpoint specific brain regions and developmental stages where Gz is transcribed or expressed. The limited tissue distribution of Gαz, its unusual biochemical properties, the identification of Gαz-specific effectors, and the inability of other Gαi subfamily members to substitute for Gαz in vivo support unique physiologic roles for Gz. The rate of GDP dissociation from Gαz is extremely slow as compared to that of most other G-protein β subunits, and almost completely suppressed at Mg2+ concentrations greater than 100 μM. Most receptors that couple to Gi proteins can also activate Gz if the G protein or receptors are overexpressed in cells. Although the precise roles of Gz in cellular signaling are still being established, accumulating evidence points to the involvement of this unique Gi subfamily member in several facets of cell biology. First, the temporal and spatial expression patterns of Gαz suggest a possible role in neuron growth and/or differentiation. Gz also appears to regulate platelet function through adrenergic receptor signaling. In addition, Gz participates in the physiologic regulation of insulin secretion from the pancreatic β cells. Finally, Gz may be involved in processes impacting on mood or behavior. These distinct roles further define Gz as unique among the Gi subfamily of heterotrimeric G proteins. © 2010 Elsevier Inc. All rights reserved.