Reactome | GABR heteropentamers:GABA transport Cl- from extracellular region to cytosol

GABR heteropentamers:GABA transport Cl- from extracellular region to cytosol

Stable Identifier

R-HSA-975340

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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GABR heteropentamers:GABA transport Cl- from extracellular region to cytosol

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The GABA(A) receptor (GABR) family belongs to the ligand-gated ion channel superfamily (LGIC). Its endogenous ligand is gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. There are six alpha subunits (GABRA) (Garrett et al. 1988, Schofield et al. 1989, Hadingham et al. 1993, Edenberg et al. 2004, Hadingham et al. 1993, Yang et al. 1995, Wingrove et al. 1992, Hadingham et al. 1996), three beta subunits (GABRB) (Schofield et al. 1989, Hadingham et al. 1993, Wagstaff et al. 1991), 2 gamma subunits (GABRG) (Khan et al. 1993, Hadingham et al. 1995) and a theta subunit (Bonnert et al. 1999) characterised to date. GABA(A) functions as a heteropentamer, the most common structure being 2 alpha subunits, 2 beta subunits and a gamma subunit (2GABRA:2GABRB:GABRG). An alternative heteropentamer with much less affinity for GABA is 2GABRA:GABRB:GABRG:GABRQ (Bonnert et al. 1999). Upon binding of GABA, both GABR complexes conduct chloride ions through their pore, resulting in hyperpolarisation of the neuron. This causes an inhibitory effect on neurotransmission by reducing the chances of a successful action potential occurring.

Literature References

PubMed ID	Title	Journal	Year
8719416	Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site Lan, NC, Yang, W, Drewe, JA	Eur J Pharmacol	1995
8391122	Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors Wingrove, P, Ragan, CI, Palmer, KJ, Hadingham, KL, Whiting, PJ, Le Bourdelles, B	Mol Pharmacol	1993
8264558	Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors Kemp, JA, Bain, C, Wingrove, PB, Ragan, CI, Palmer, KJ, Wafford, KA, Hadingham, KL, Sikela, JM, Wilcox, AS, Wilson, AW	Mol Pharmacol	1993
19828786	Extrasynaptic GABAA receptors: form, pharmacology, and function Cope, DW, Maguire, J, Harrison, NL, Belelli, D, Walker, MC, Macdonald, RL	J Neurosci	2009
8719414	Expression and pharmacology of human GABAA receptors containing gamma 3 subunits Palmer, KJ, Wafford, KA, Hadingham, KL, Whiting, PJ, Thompson, SA	Eur J Pharmacol	1995
17364682	GABAA receptors: properties and trafficking Michels, G, Moss, SJ	Crit Rev Biochem Mol Biol	2007
8632757	Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors Bain, C, Heavens, RP, Sirinathsinghji, DJ, Garrett, EM, Wafford, KA, Hadingham, KL, Whiting, PJ	Mol Pharmacol	1996
18382465	GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition Moss, SJ, Jacob, TC, Jurd, R	Nat Rev Neurosci	2008
2847710	Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor Duman, RS, Tallman, JF, Blume, AJ, Saito, N, Garrett, KM, Vitek, MP	Biochem Biophys Res Commun	1988
8382267	Antibodies to the human gamma 2 subunit of the gamma-aminobutyric acidA/benzodiazepine receptor Fernando, LP, Mallet, J, Busquets, X, Khan, ZU, De Blas, AL, Filla, M, Escribá, P, Miralles, CP	J Neurochem	1993
10449790	theta, a novel gamma-aminobutyric acid type A receptor subunit Whiting, PJ, Bonnert, TP, Heavens, RP, le Bourdellès, B, Farrar, S, McKernan, RM, Hewson, L, Rigby, MR, Wafford, KA, Sirinathsinghji, DJ, Smith, DW, Brown, N	Proc. Natl. Acad. Sci. U.S.A.	1999
1664410	The GABAA receptor beta 3 subunit gene: characterization of a human cDNA from chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7 Wagstaff, J, Lalande, M, Chaillet, JR	Genomics	1991
15024690	Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations Kwon, J, Nurnberger JI, Jr, Reich, T, O'Connor, SJ, Begleiter, H, Jones, K, Li, TK, Tian, H, Edenberg, HJ, Rice, J, Xuei, X, Crowe, RR, Bauer, LO, Goate, A, Dick, DM, Porjesz, B, Foroud, T, Almasy, L, Schuckit, MA, Hesselbrock, V	Am J Hum Genet	2004
1321750	Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit Kemp, JA, Hadingham, K, Wingrove, P, Ragan, CI, Wafford, K, Whiting, P	Biochem Soc Trans	1992
2465923	Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits Kettenmann, H, Pritchett, DB, Schofield, PR, Seeburg, PH, Sontheimer, H	FEBS Lett	1989