Gi alpha subunit

From Wikipedia, the free encyclopedia
  (Redirected from Gαi)
Jump to navigation Jump to search
G protein subunit alpha i1
Identifiers
SymbolGNAI1
NCBI gene2770
HGNC4384
OMIM139310
PDB3UMR
RefSeqNM_002069
UniProtP63096
Other data
LocusChr. 7 q21-q22
G protein subunit alpha i2
Identifiers
SymbolGNAI2
NCBI gene2771
HGNC4385
OMIM139360
RefSeqNM_002070
UniProtP04899
Other data
LocusChr. 3 p21
G protein subunit alpha i3
Identifiers
SymbolGNAI3
NCBI gene2773
HGNC4387
OMIM139370
PDB2ODE
RefSeqNM_006496
UniProtP08754
Other data
LocusChr. 1 p13
G protein subunit alpha o1
Identifiers
SymbolGNAO1
NCBI gene2775
HGNC4389
OMIM139311
RefSeqNM_020988
UniProtP09471,
Other data
LocusChr. 16 q13
G protein subunit alpha z
Identifiers
SymbolGNAZ
NCBI gene2781
HGNC4395
OMIM139160
RefSeqNM_002073
UniProtP19086
Other data
LocusChr. 22 q11.22-11.23
G protein subunit alpha t1, Transducin 1 (rod)
Identifiers
SymbolGNAT1
NCBI gene2779
HGNC4393
OMIM139330
RefSeqNM_000172
UniProtP11488
Other data
LocusChr. 3 p21.31
G protein subunit alpha t2, Transducin 2 (cone)
Identifiers
SymbolGNAT2
NCBI gene2780
HGNC4394
OMIM139340
RefSeqNM_005272
UniProtP19087
Other data
LocusChr. 1 p13.3
G protein subunit alpha t3, Gustducin
Identifiers
SymbolGNAT3
NCBI gene346562
HGNC22800
OMIM139395
RefSeqNM_001102386
UniProtA8MTJ3
Other data
LocusChr. 7 q21.11

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

Family members[edit]

There are four distinct subtypes of alpha subunits in the Gi/o/z/t alpha subunit family that define four families of heterotrimeric G proteins:

  • Gi proteins: Gi1α, Gi2α, and Gi3α
  • Go protein: Goα (in mouse there is alternative splicing to generate Go1α and Go2α)
  • Gz protein: Gzα
  • Transducins (Gt proteins): Gt1α, Gt2α, Gt3α

Giα proteins[edit]

Gi1α[edit]

Gi1α is encoded by the gene GNAI1.

Gi2α[edit]

Gi2α is encoded by the gene GNAI2.

Gi3α[edit]

Gi3α is encoded by the gene GNAI3.

Goα protein[edit]

Go1α is encoded by the gene GNAO1.

Gzα protein[edit]

Gzα is encoded by the gene GNAZ.

Transducin proteins[edit]

Gt1α[edit]

Transducin/Gt1α is encoded by the gene GNAT1.

Gt2α[edit]

Transducin 2/Gt2α is encoded by the gene GNAT2.

Gt3α[edit]

Gustducin/Gt3α is encoded by the gene GNAT3.

Function[edit]

The general function of Gi/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.[1][2] The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα protein such as Giα, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex.[1][2] When not stimulated by a receptor, Gα is bound to GDP and to Gβγ to form the inactive G protein trimer.[1][2] 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.[1][2] GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.

Gi 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 Gi is the opposite of cAMP-dependent protein kinase. The Gβγ liberated by activation of Gi and Go proteins is particularly able to activate downstream signaling to effectors such as G protein-coupled inwardly-rectifying potassium channels (GIRKs).[3] Gi and Go 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 one particular cysteine residue in Giα and Goα proteins, preventing their coupling to and activation by GPCRs, thus turning off Gi and Go cell signaling pathways.[4]

Gz proteins also can link GPCRs to inhibition of adenylyl cyclase, but Gz is distinct from Gi/Go by being insensitive to inhibition by pertussis toxin.[5]

Gt proteins function in sensory transduction. The Transducins Gt1 and Gt2 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 Gt1, and color photopsins in color vision in retinal cone cells couple to Gt2, respectively. Gt3/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]

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

See also[edit]

References[edit]

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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: acsptsci.9b00049. doi:10.1021/acsptsci.9b00049.

External links[edit]