G<sub>i</sub> protein alpha subunit is a family of heterotrimeric G protein alpha subunits. G<sub>i</sub> proteins primarily inhibit the cAMP dependent pathway by inhibiting adenylyl cyclase activity, resulting in decreased activity of cAMP-dependent protein kinase (PKA). This family is also commonly called the G<sub>i/o</sub> (G<sub>i </sub>/G<sub>o </sub>) family or G<sub>i/o/z/t</sub> family to include closely related family members. G alpha subunits may be referred to as G<sub>i</sub> alpha, G<sub>ñi</sub>, or G<sub>i</sub>ñ.
There are four distinct subtypes of alpha subunits in the G<sub>i/o/z/t</sub> alpha subunit family that define four families of heterotrimeric G proteins:
G<sub>i1</sub>ñ is encoded by the gene GNAI1.
G<sub>i2</sub>ñ is encoded by the gene GNAI2.
G<sub>i3</sub>ñ is encoded by the gene GNAI3.
G<sub>o1</sub>ñ is encoded by the gene GNAO1.
G<sub>z</sub>ñ is encoded by the gene GNAZ.
Transducin/G<sub>t1</sub>ñ is encoded by the gene GNAT1.
Transducin 2/G<sub>t2</sub>ñ is encoded by the gene GNAT2.
Gustducin/G<sub>t3</sub>ñ is encoded by the gene GNAT3.
The general function of G<sub>i/o/z/t</sub> is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gñ protein such as G<sub>i</sub>ñ, and a complex of two tightly linked proteins called Gò and Gó in a Gòó complex. When not stimulated by a receptor, Gñ is bound to GDP and to Gòó to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a hormone or neurotransmitter), the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and GTP binding to Gñ, which drives dissociation of GTP-bound Gñ from Gòó. GTP-bound Gñ and Gòó are then freed to activate their respective downstream signaling enzymes.
G<sub>i</sub> proteins primarily inhibit the cAMP dependent pathway by inhibiting adenylyl cyclase activity, decreasing the production of cAMP from ATP, which, in turn, results in decreased activity of cAMP-dependent protein kinase. Therefore, the ultimate effect of G<sub>i</sub> is the inhibition of the cAMP-dependent protein kinase. The Gòó liberated by activation of G<sub>i</sub> and G<sub>o</sub> proteins is particularly able to activate downstream signaling to effectors such as G protein-coupled inwardly-rectifying potassium channels (GIRKs). G<sub>i</sub> and G<sub>o</sub> proteins are substrates for pertussis toxin, produced by Bordetella pertussis, the infectious agent in whooping cough. Pertussis toxin is an ADP-ribosylase enzyme that adds an ADP-ribose moiety to a particular cysteine residue in G<sub>i</sub>ñ and G<sub>o</sub>ñ proteins, preventing their coupling to and activation by GPCRs, thus turning off G<sub>i</sub> and G<sub>o</sub> cell signaling pathways.
G<sub>z</sub> proteins also can link GPCRs to inhibition of adenylyl cyclase, but G<sub>z</sub> is distinct from G<sub>i</sub>/G<sub>o</sub> by being insensitive to inhibition by pertussis toxin.
G<sub>t</sub> proteins function in sensory transduction. The Transducins G<sub>t1</sub> and G<sub>t2</sub> serve to transduce signals from G protein-coupled receptors that receive light during vision. Rhodopsin in dim light night vision in retinal rod cells couples to G<sub>t1</sub>, and color photopsins in color vision in retinal cone cells couple to G<sub>t2</sub>, respectively. G<sub>t3</sub>/Gustducin subunits transduce signals in the sense of taste (gustation) in taste buds by coupling to G protein-coupled receptors activated by sweet or bitter substances.
The following G protein-coupled receptors couple to G<sub>i/o</sub> subunits: