Gαi protein subunit: A step toward understanding its non-canonical mechanisms

The heterotrimeric G protein family plays essential roles during a varied array of cellular events; thus, its deregulation can seriously alter signaling events and the overall state of the cell. Heterotrimeric G-proteins have three subunits (alpha, beta, gamma) and are subdivided into four families, G alpha i, G alpha 12/13, G alpha q, and G alpha s. These proteins cycle between an inactive G alpha-GDP state and active G alpha-GTP state, triggered canonically by the G-protein coupled receptor (GPCR) and by other accessory proteins receptors independent also known as AGS (Activators of G-protein Signaling). In this review, we summarize research data specific for the G alpha i family. This family has the largest number of individual members, including G alpha i1, G alpha i2, G alpha i3, G alpha o, G alpha t, G alpha g, and G alpha z, and constitutes the majority of G proteins alpha subunits expressed in a tissue or cell. G alpha i was initially described by its inhibitory function on adenylyl cyclase activity, decreasing cAMP levels. Interestingly, today Gi family G-protein have been reported to be importantly involved in the immune system function. Here, we discuss the impact of G alpha i on non-canonical effector proteins, such as c-Src, ERK1/2, phospholipase-C (PLC), and proteins from the Rho GTPase family members, all of them essential signaling pathways regulating a wide range of physiological processes.

Automated summary

The heterotrimeric G protein family plays essential roles in cellular events, and its deregulation can greatly impact cell signaling and function. The Gαi family, with its numerous members, has been found to be important in immune system function.