GTP-binding proteins in cell survival and demise: the emerging picture in the pancreatic β-cell

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It is widely believed that guanine nucleotide-binding regulatory proteins (G-proteins) play central roles as “molecular switches” in a variety of cellular processes ranging from signal transduction to protein and vesicle trafficking. To achieve these regulatory functions, G-proteins form complexes with a wide range of effector molecules whose activities are altered upon interaction with the G-protein. These effector molecules can be either soluble or membrane bound, and it is likely that some are localized to secretory granules where they direct the movement, docking, and fusion of granules during exocytosis. The effector molecules regulated by G-proteins are diverse and include phospholipases, protein kinases, protein phosphatases, ion channels, adenylate cyclases, cytoskeletal elements, as well as secretory vesicle and plasma membrane-associated fusion-proteins. The majority of studies performed in the pancreatic β-cell have focused on the role of G-proteins in the regulation of insulin secretion, whereas very little attention has been focused on their potential involvement in other cellular processes. Such studies have identified and implicated both heterotrimeric (comprising α, β, and γ subunits) and monomeric (low molecular mass) G-proteins in the regulation of insulin secretion, but intriguing recent evidence has also begun to emerge which favors the view that they may be involved in the maintenance of β-cell viability. In the present commentary, we will review this evidence and discuss the current understanding of the role of G-proteins in the life and death of the β-cell.