G is a family of i protein alpha subunit heterotrimeric G protein alpha subunits. This family is also commonly called the G ( i/o G) family or i /G o G family to include closely related family members. G alpha subunits may be referred to as G i/o/z/t i alpha, G αi, or G iα.
Family members [ edit ]
There are four distinct subtypes of alpha subunits in the G
i/o/z/t alpha subunit family that define four families of heterotrimeric G proteins:
i proteins: G i1α, G i2α, and G i3α G
o protein: G oα (in mouse there is alternative splicing to generate G o1α and G o2α) G
z protein: G zα Transducins (G t proteins): G t1α, G t2α, G t3α
G iα proteins [ edit ]
i1α is encoded by the gene GNAI1.
i2α is encoded by the gene GNAI2.
i3α is encoded by the gene GNAI3.
G oα protein [ edit ]
o1α is encoded by the gene GNAO1.
G zα protein [ edit ]
zα is encoded by the gene GNAZ.
Transducin proteins [ edit ]
Transducin/G t1α is encoded by the gene GNAT1.
t2α is encoded by the gene GNAT2.
Gustducin/G t3α is encoded by the gene GNAT3.
Function [ edit ]
The general function of G
i/o/z/t 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 Gα protein such as G iα, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex.  When not stimulated by a receptor, Gα is bound to  GDP and to Gβγ 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 Gα, which drives dissociation of GTP-bound Gα from Gβγ.  GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.
i 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 i is the inhibition of the cAMP-dependent protein kinase. The Gβγ liberated by activation of G i and G o proteins is particularly able to activate downstream signaling to effectors such as G protein-coupled inwardly-rectifying potassium channels (GIRKs). G  i and G o 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 iα and G oα proteins, preventing their coupling to and activation by GPCRs, thus turning off G i and G o cell signaling pathways.
z proteins also can link GPCRs to inhibition of adenylyl cyclase, but G z is distinct from G i/G o by being insensitive to inhibition by pertussis toxin.
t proteins function in sensory transduction. The Transducins G t1 and G t2 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 t1, and color photopsins in color vision in retinal cone cells couple to G t2, respectively. G t3/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.
Receptors [ edit ]
G protein-coupled receptors couple to G i/o subunits:
Acetylcholine M & 2 M receptors 4
Adenosine A & 1 A receptors 3
Adrenergic α, 2A α, & 2B α receptors 2C
Cannabinoid receptors ( CB1 and CB2 ) 
Chemokine CXCR4 receptor
Dopamine D, 2 D, 3 D 4
GABA receptor B
Glutamate mGlu, 2 mGlu, 3 mGlu, 4 mGlu, 6 mGlu, & 7 mGlu receptors 8
Histamine H & 3 H receptors 4
Melatonin MT, 1 MT, & 2 MT receptors 3
Hydroxycarboxylic acid receptors: HCA1, HCA2, & HCA3
Opioid δ, κ, μ, & nociceptin receptors
Prostaglandin EP, 1 EP, 3 FP, & TP receptors
Serotonin 5-HT & 1 5-HT receptors 5
Short chain fatty acid receptors: FFAR2 & FFAR3
Somatostatin sst1, sst2, sst3, sst4 & sst5 receptors Trace amine-associated receptor 8
See also [ edit ]
References [ edit ]
^ a b c d
Gilman AG (1987). "G proteins: transducers of receptor-generated signals". Annual Review of Biochemistry. 56: 615–49. doi: 10.1146/annurev.bi.56.070187.003151. PMID 3113327.
^ a b c d
Rodbell M (June 1995). "Nobel Lecture. Signal transduction: evolution of an idea". Bioscience Reports. 15 (3): 117–33. doi: 10.1007/bf01207453. PMID 7579038. S2CID 11025853.
Kano H, Toyama Y, Imai S, Iwahashi Y, Mase Y, Yokogawa M, et al. (May 2019). "Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel". Nature Communications. 10 (1): 2008. Bibcode: 2019NatCo..10.2008K. doi: 10.1038/s41467-019-10038-x. PMC . 6494913 PMID 31043612.
Pfeuffer T, Helmreich EJ (1988). "Structural and functional relationships of guanosine triphosphate binding proteins". Current Topics in Cellular Regulation. 29: 129–216. doi: 10.1016/B978-0-12-152829-4.50006-9. ISBN . 9780121528294 PMID 3135154.
Ho MK, Wong YH (March 2001). "G(z) signaling: emerging divergence from G(i) signaling". Oncogene. 20 (13): 1615–25. doi: . 10.1038/sj.onc.1204190 PMID 11313909.
Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL (2019-10-19). "Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes". ACS Pharmacology & Translational Science. 2 (6): 414–428. doi: . 10.1021/acsptsci.9b00049 PMC . 7088898 PMID 32259074.
External links [ edit ]