Gi alpha subunit explained

G protein subunit alpha i1
Hgncid:4384
Symbol:GNAI1
Entrezgene:2770
Omim:139310
Refseq:NM_002069
Uniprot:P63096
Pdb:3UMR
Chromosome:7
Arm:q
Band:21
Locussupplementarydata:-q22
G protein subunit alpha i2
Hgncid:4385
Symbol:GNAI2
Entrezgene:2771
Omim:139360
Refseq:NM_002070
Uniprot:P04899
Chromosome:3
Arm:p
Band:21
G protein subunit alpha i3
Hgncid:4387
Symbol:GNAI3
Entrezgene:2773
Omim:139370
Refseq:NM_006496
Uniprot:P08754
Pdb:2ODE
Chromosome:1
Arm:p
Band:13
G protein subunit alpha o1
Hgncid:4389
Symbol:GNAO1
Entrezgene:2775
Omim:139311
Refseq:NM_020988
Uniprot:P09471,
Chromosome:16
Arm:q
Band:13
G protein subunit alpha z
Hgncid:4395
Symbol:GNAZ
Entrezgene:2781
Omim:139160
Refseq:NM_002073
Uniprot:P19086
Chromosome:22
Arm:q
Band:11.22-11.23
G protein subunit alpha t1, Transducin 1 (rod)
Hgncid:4393
Symbol:GNAT1
Entrezgene:2779
Omim:139330
Refseq:NM_000172
Uniprot:P11488
Chromosome:3
Arm:p
Band:21.31
G protein subunit alpha t2, Transducin 2 (cone)
Hgncid:4394
Symbol:GNAT2
Entrezgene:2780
Omim:139340
Refseq:NM_005272
Uniprot:P19087
Chromosome:1
Arm:p
Band:13.3
G protein subunit alpha t3, Gustducin
Hgncid:22800
Symbol:GNAT3
Entrezgene:346562
Omim:139395
Refseq:NM_001102386
Uniprot:A8MTJ3
Chromosome:7
Arm:q
Band:21.11

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

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:

Giα proteins

Gi1α

Gi1α is encoded by the gene GNAI1.

Gi2α

Gi2α is encoded by the gene GNAI2.

Gi3α

Gi3α is encoded by the gene GNAI3.

Goα protein

Go1α is encoded by the gene GNAO1.

Gzα protein

Gzα is encoded by the gene GNAZ.

Transducin proteins

See main article: Transducin.

Gt1α

Transducin/Gt1α is encoded by the gene GNAT1.

Gt2α

Transducin 2/Gt2α is encoded by the gene GNAT2.

Gt3α

See main article: Gustducin. Gustducin/Gt3α is encoded by the gene GNAT3.

Function

See main article: Heterotrimeric G protein. 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 inhibition of the 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 to a 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

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

See also

Notes and References

  1. Gilman AG . G proteins: transducers of receptor-generated signals . Annual Review of Biochemistry . 56 . 615–49 . 1987 . 3113327 . 10.1146/annurev.bi.56.070187.003151 .
  2. Rodbell M . Nobel Lecture. Signal transduction: evolution of an idea . Bioscience Reports . 15 . 3 . 117–33 . June 1995 . 7579038 . 10.1007/bf01207453 . 11025853 . 1519115 .
  3. Kano H, Toyama Y, Imai S, Iwahashi Y, Mase Y, Yokogawa M, Osawa M, Shimada I . 6 . Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel . Nature Communications . 10 . 1 . 2008 . May 2019 . 31043612 . 6494913 . 10.1038/s41467-019-10038-x . 2019NatCo..10.2008K .
  4. Pfeuffer T, Helmreich EJ . Structural and functional relationships of guanosine triphosphate binding proteins . Current Topics in Cellular Regulation . 29 . 129–216 . 1988 . 3135154 . 10.1016/B978-0-12-152829-4.50006-9 . 9780121528294 .
  5. Ho MK, Wong YH . G(z) signaling: emerging divergence from G(i) signaling . Oncogene . 20 . 13 . 1615–25 . March 2001 . 11313909 . 10.1038/sj.onc.1204190 . free .