Gi Alpha Subunit

G_i protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the G_i/o (G_i /G_o ) family or G_i/o/z/t family to include closely related family members. G alpha subunits may be referred to as G_i alpha, G_αi, or G_iα.

Family members

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:
* G_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

G_i1α

G_i1α is encoded by the gene GNAI1.

G_i2α

G_i2α is encoded by the gene GNAI2.

G_i3α

G_i3α is encoded by the gene GNAI3.

G_oα protein

G_o1α is encoded by the gene GNAO1.

G_zα protein

G_zα is encoded by the gene GNAZ.

Transducin proteins

G_t1α

Transducin/G_t1α is encoded by the gene GNAT1.

G_t2α

Transducin 2/G_t2α is encoded by the gene GNAT2.

G_t3α

Gustducin/G_t3α is encoded by the gene GNAT3.

Function

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.

G_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.

G_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.

G_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

The following G protein-coupled receptors couple to G_i/o subunits:

* Acetylcholine M₂ & M₄ receptors
* Adenosine A₁ & A₃ receptors
* Adrenergic α_2A, α_2B, & α_2C receptors
* Apelin receptors
* Calcium-sensing receptor
* Cannabinoid receptors ( CB1 and CB2)
* Chemokine CXCR4 receptor
* Dopamine D₂, D₃, D₄
* GABA_B receptor
* Glutamate mGlu₂, mGlu₃, mGlu₄, mGlu₆, mGlu₇, & mGlu₈ receptors
* Histamine H₃ & H₄ receptors
* Melatonin MT₁, MT₂, & MT₃ receptors
* Hydroxycarboxylic acid receptors: HCA1, HCA2, & HCA3
* Opioid δ, κ, μ, & nociceptin receptors
* Prostaglandin EP₁, EP₃, FP, & TP receptors
* Serotonin 5-HT₁ & 5-HT₅ receptors
* Short chain fatty acid receptors: FFAR2 & FFAR3
* Somatostatin sst1, sst2, sst3, sst4 & sst5 receptors
* Trace amine-associated receptor 8

See also

* Second messenger system
* G protein-coupled receptor
* Heterotrimeric G protein
* Adenylyl cyclase
* Protein kinase A
* Gs alpha subunit
* Gq alpha subunit
* G12/G13 alpha subunits
* Retina
* Taste

References

External links

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Peripheral membrane proteins