GABA receptor activation (Homo sapiens)

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3, 7, 8, 10, 30315, 16, 213118, 20, 2312, 261, 2, 4, 6, 11...279, 22, 24, 2931cytosolKCNJ6 GABBR1 GNAI2 ADCY9 ADCY1 GNAT3 GNAI3 ADCY6 GDP GABRA6 KCNJ3 GABRA4 KCNJ9 (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ADCY5 ADCY7 GABRA2 (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ADCY8 GNAL G alpha-olf:GDPcomplexGNG12 ADCY3 GABRB3 GNAL ARHGEF9 GNAT3 GABRheteropentamers:GABA:NPTNGABRheteropentamers:GABAGNG8 ADCY8 ADCY3 ADCY6 ADCY4 GABRA6 Cl-GNAI2 ADCY9 GABRG3 GABA GABRG2 NPTNGNAT3 GABRR1 GABA GABBR2 Cl-GNB3 GABBR1 ADCY2 GNGT1 ADCY5 GTP ADCY1 ADCY3 Mg2+ GDP GNAL GABRA4 G-protein alpha(i):GTP:AdenylatecyclaseADCY9 ADCY7 GNGT2 ADCY3 GABRR pentamer:GABAGNAI2 GNAI1 GABRR2 ADCY5 ARHGEF9 ADCY8 KCNJ10 NPTN GABRR3 GABRB2 GNG3 GTP GABA GABRA3 (Gialpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)Mg2+ GNAL ADCY7 ADCY2 KCNJ15 ADCY4 ADCY9 KCNJ2 GNAI2 GABRB1 GABA B receptorG-proteinbeta-gamma and Kir3channel complexGDP K+GNG10 GABAB receptor:GABAADCY6 ADCY7 ADCY2 GABRA5 GABRB2 GNAI2 GABRQ GNAI3 GNAI1 GTP GNB1 GABRQ GABRB1 ADCY7 GNAI3 GTP G alpha (i): GTPGABRA1 ADCY9 GABBR2 GNG2 ADCY6 GNAI1 ADCY2 ADCY8 Adenylate cyclase(Mg2+ cofactor)GNG5 K+ADCY4 KCNJ16 GNG4 ADCY1 GNAT3 GABRB3 GNAT3 Mg2+ GNAI3 GABA GABRA3 GNAT3 ADCY1 GDP GABAG alpha-olf:GTPADCY3 ADCY1 GNAI1 GABRG3 KCNJ12 GNAI1 Mg2+ GABAB receptorKCNJ5 GABRA2 G-protein alpha(i):GDPGNAI1 GABBR1 GNAI2 GABRA1 ADCY4 ADCY4 GNB2 PiADCY5 GABRA5 GDP GABA GNAI3 GNG7 ADCY5 ADCY8 KCNJ4 ADCY2 GABRG2 Mg2+ GNAL GABBR2 GNAI3 GTP ADCY6


Description

Gamma aminobutyric acid (GABA) receptors are the major inhibitory receptors in human synapses. They are of two types. GABA A receptors are fast-acting ligand gated chloride ion channels that mediate membrane depolarization and thus inhibit neurotransmitter release (G Michels et al Crit Rev Biochem Mol Biol 42, 2007, 3-14). GABA B receptors are slow acting metabotropic Gprotein coupled receptors that act via the inhibitory action of their Galpha/Go subunits on adenylate cyclase to attenuate the actions of PKA. In addition, their Gbeta/gamma subunits interact directly with N and P/Q Ca2+ channels to decrease the release of Ca2+. GABA B receptors also interact with Kir3 K+ channels and increase the influx of K+, leading to cell membrane hyperpolarization and inhibition of channels such as NMDA receptors (A Pinard et al Adv Pharmacol, 58, 2010, 231-55). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 977443
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Mahajan, SS

Quality Tags

Ontology Terms

 

Bibliography

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  1. Hadingham KL, Wingrove PB, Wafford KA, Bain C, Kemp JA, Palmer KJ, Wilson AW, Wilcox AS, Sikela JM, Ragan CI.; ''Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors.''; PubMed Europe PMC
  2. Hadingham KL, Garrett EM, Wafford KA, Bain C, Heavens RP, Sirinathsinghji DJ, Whiting PJ.; ''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.''; PubMed Europe PMC
  3. Moss SJ, Smart TG.; ''Constructing inhibitory synapses.''; PubMed Europe PMC
  4. Hadingham KL, Wingrove P, Le Bourdelles B, Palmer KJ, Ragan CI, Whiting PJ.; ''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.''; PubMed Europe PMC
  5. Clark MJ, Traynor JR.; ''Mediation of adenylyl cyclase sensitization by PTX-insensitive GalphaoA, Galphai1, Galphai2 or Galphai3.''; PubMed Europe PMC
  6. Edenberg HJ, Dick DM, Xuei X, Tian H, Almasy L, Bauer LO, Crowe RR, Goate A, Hesselbrock V, Jones K, Kwon J, Li TK, Nurnberger JI, O'Connor SJ, Reich T, Rice J, Schuckit MA, Porjesz B, Foroud T, Begleiter H.; ''Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.''; PubMed Europe PMC
  7. Pinard A, Seddik R, Bettler B.; ''GABAB receptors: physiological functions and mechanisms of diversity.''; PubMed Europe PMC
  8. Padgett CL, Slesinger PA.; ''GABAB receptor coupling to G-proteins and ion channels.''; PubMed Europe PMC
  9. Bailey ME, Albrecht BE, Johnson KJ, Darlison MG.; ''Genetic linkage and radiation hybrid mapping of the three human GABA(C) receptor rho subunit genes: GABRR1, GABRR2 and GABRR3.''; PubMed Europe PMC
  10. Bettler B, Kaupmann K, Mosbacher J, Gassmann M.; ''Molecular structure and physiological functions of GABA(B) receptors.''; PubMed Europe PMC
  11. Wagstaff J, Chaillet JR, Lalande M.; ''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.''; PubMed Europe PMC
  12. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH.; ''Heterodimerization is required for the formation of a functional GABA(B) receptor.''; PubMed Europe PMC
  13. Yang W, Drewe JA, Lan NC.; ''Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site.''; PubMed Europe PMC
  14. Wingrove P, Hadingham K, Wafford K, Kemp JA, Ragan CI, Whiting P.; ''Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit.''; PubMed Europe PMC
  15. Khan ZU, Fernando LP, Escribá P, Busquets X, Mallet J, Miralles CP, Filla M, De Blas AL.; ''Antibodies to the human gamma 2 subunit of the gamma-aminobutyric acidA/benzodiazepine receptor.''; PubMed Europe PMC
  16. Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE.; ''The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells.''; PubMed Europe PMC
  17. Hadingham KL, Wafford KA, Thompson SA, Palmer KJ, Whiting PJ.; ''Expression and pharmacology of human GABAA receptors containing gamma 3 subunits.''; PubMed Europe PMC
  18. Taussig R, Tang WJ, Hepler JR, Gilman AG.; ''Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases.''; PubMed Europe PMC
  19. Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH.; ''Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits.''; PubMed Europe PMC
  20. Dessauer CW, Chen-Goodspeed M, Chen J.; ''Mechanism of Galpha i-mediated inhibition of type V adenylyl cyclase.''; PubMed Europe PMC
  21. Gerhardt MA, Neubig RR.; ''Multiple Gi protein subtypes regulate a single effector mechanism.''; PubMed Europe PMC
  22. Cutting GR, Lu L, O'Hara BF, Kasch LM, Montrose-Rafizadeh C, Donovan DM, Shimada S, Antonarakis SE, Guggino WB, Uhl GR.; ''Cloning of the gamma-aminobutyric acid (GABA) rho 1 cDNA: a GABA receptor subunit highly expressed in the retina.''; PubMed Europe PMC
  23. Taussig R, Iñiguez-Lluhi JA, Gilman AG.; ''Inhibition of adenylyl cyclase by Gi alpha.''; PubMed Europe PMC
  24. Zhu Y, Ripps H, Qian H.; ''A single amino acid in the second transmembrane domain of GABA rho receptors regulates channel conductance.''; PubMed Europe PMC
  25. Garrett KM, Duman RS, Saito N, Blume AJ, Vitek MP, Tallman JF.; ''Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor.''; PubMed Europe PMC
  26. Kaupmann K, Schuler V, Mosbacher J, Bischoff S, Bittiger H, Heid J, Froestl W, Leonhard S, Pfaff T, Karschin A, Bettler B.; ''Human gamma-aminobutyric acid type B receptors are differentially expressed and regulate inwardly rectifying K+ channels.''; PubMed Europe PMC
  27. Fowler CE, Aryal P, Suen KF, Slesinger PA.; ''Evidence for association of GABA(B) receptors with Kir3 channels and regulators of G protein signalling (RGS4) proteins.''; PubMed Europe PMC
  28. Bonnert TP, McKernan RM, Farrar S, le Bourdellès B, Heavens RP, Smith DW, Hewson L, Rigby MR, Sirinathsinghji DJ, Brown N, Wafford KA, Whiting PJ.; ''theta, a novel gamma-aminobutyric acid type A receptor subunit.''; PubMed Europe PMC
  29. Cutting GR, Curristin S, Zoghbi H, O'Hara B, Seldin MF, Uhl GR.; ''Identification of a putative gamma-aminobutyric acid (GABA) receptor subunit rho2 cDNA and colocalization of the genes encoding rho2 (GABRR2) and rho1 (GABRR1) to human chromosome 6q14-q21 and mouse chromosome 4.''; PubMed Europe PMC
  30. Michels G, Moss SJ.; ''GABAA receptors: properties and trafficking.''; PubMed Europe PMC
  31. Kleuss C, Raw AS, Lee E, Sprang SR, Gilman AG.; ''Mechanism of GTP hydrolysis by G-protein alpha subunits.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
102016view15:12, 26 November 2018Marvin M2Ontology Term : 'neuron' added !
102015view15:10, 26 November 2018Marvin M2Ontology Term : 'gamma-aminobutyric acid signaling pathway' added !
102014view15:08, 26 November 2018Marvin M2Ontology Term : 'PW:0000003' removed !
101668view13:48, 1 November 2018DeSlOntology Term : 'signaling pathway' added !
101658view11:51, 1 November 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170656 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170659 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ComplexR-HSA-170683 (Reactome)
ADCY1 ProteinQ08828 (Uniprot-TrEMBL)
ADCY2 ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 ProteinO60266 (Uniprot-TrEMBL)
ADCY4 ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 ProteinO95622 (Uniprot-TrEMBL)
ADCY6 ProteinO43306 (Uniprot-TrEMBL)
ADCY7 ProteinP51828 (Uniprot-TrEMBL)
ADCY8 ProteinP40145 (Uniprot-TrEMBL)
ADCY9 ProteinO60503 (Uniprot-TrEMBL)
ARHGEF9 ProteinO43307 (Uniprot-TrEMBL)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (Reactome)
Cl-MetaboliteCHEBI:17996 (ChEBI)
G alpha (i): GTPComplexR-HSA-392161 (Reactome)
G alpha-olf:GDP complexComplexR-HSA-170669 (Reactome)
G alpha-olf:GTPComplexR-HSA-170661 (Reactome)
G-protein alpha (i):GDPComplexR-HSA-392164 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ComplexR-HSA-396910 (Reactome)
GABA B receptor

G-protein beta-gamma and Kir3

channel complex
ComplexR-HSA-1013011 (Reactome)
GABA MetaboliteCHEBI:59888 (ChEBI)
GABAB receptor:GABAComplexR-HSA-420698 (Reactome)
GABAB receptorComplexR-HSA-420748 (Reactome)
GABAMetaboliteCHEBI:59888 (ChEBI)
GABBR1 ProteinQ9UBS5 (Uniprot-TrEMBL)
GABBR2 ProteinO75899 (Uniprot-TrEMBL)
GABR heteropentamers:GABA:NPTNComplexR-HSA-8856431 (Reactome)
GABR heteropentamers:GABAComplexR-HSA-975268 (Reactome)
GABRA1 ProteinP14867 (Uniprot-TrEMBL)
GABRA2 ProteinP47869 (Uniprot-TrEMBL)
GABRA3 ProteinP34903 (Uniprot-TrEMBL)
GABRA4 ProteinP48169 (Uniprot-TrEMBL)
GABRA5 ProteinP31644 (Uniprot-TrEMBL)
GABRA6 ProteinQ16445 (Uniprot-TrEMBL)
GABRB1 ProteinP18505 (Uniprot-TrEMBL)
GABRB2 ProteinP47870 (Uniprot-TrEMBL)
GABRB3 ProteinP28472 (Uniprot-TrEMBL)
GABRG2 ProteinP18507 (Uniprot-TrEMBL)
GABRG3 ProteinQ99928 (Uniprot-TrEMBL)
GABRQ ProteinQ9UN88 (Uniprot-TrEMBL)
GABRR pentamer:GABAComplexR-HSA-975448 (Reactome)
GABRR1 ProteinP24046 (Uniprot-TrEMBL)
GABRR2 ProteinP28476 (Uniprot-TrEMBL)
GABRR3 ProteinA8MPY1 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GNAI1 ProteinP63096 (Uniprot-TrEMBL)
GNAI2 ProteinP04899 (Uniprot-TrEMBL)
GNAI3 ProteinP08754 (Uniprot-TrEMBL)
GNAL ProteinP38405 (Uniprot-TrEMBL)
GNAT3 ProteinA8MTJ3 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
K+MetaboliteCHEBI:29103 (ChEBI)
KCNJ10 ProteinP78508 (Uniprot-TrEMBL)
KCNJ12 ProteinQ14500 (Uniprot-TrEMBL)
KCNJ15 ProteinQ99712 (Uniprot-TrEMBL)
KCNJ16 ProteinQ9NPI9 (Uniprot-TrEMBL)
KCNJ2 ProteinP63252 (Uniprot-TrEMBL)
KCNJ3 ProteinP48549 (Uniprot-TrEMBL)
KCNJ4 ProteinP48050 (Uniprot-TrEMBL)
KCNJ5 ProteinP48544 (Uniprot-TrEMBL)
KCNJ6 ProteinP48051 (Uniprot-TrEMBL)
KCNJ9 ProteinQ92806 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NPTN ProteinQ9Y639 (Uniprot-TrEMBL)
NPTNProteinQ9Y639 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170686 (Reactome)
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)R-HSA-170674 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ArrowR-HSA-170671 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170686 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170686 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowR-HSA-170674 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-392206 (Reactome)
Cl-ArrowR-HSA-975340 (Reactome)
Cl-ArrowR-HSA-975449 (Reactome)
Cl-R-HSA-975340 (Reactome)
Cl-R-HSA-975449 (Reactome)
G alpha (i): GTPR-HSA-392206 (Reactome)
G alpha-olf:GDP complexArrowR-HSA-170674 (Reactome)
G alpha-olf:GTPR-HSA-170671 (Reactome)
G-protein alpha (i):GDPArrowR-HSA-170674 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ArrowR-HSA-392206 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
R-HSA-170671 (Reactome)
GABA B receptor

G-protein beta-gamma and Kir3

channel complex
mim-catalysisR-HSA-1013020 (Reactome)
GABAB receptor:GABAArrowR-HSA-420688 (Reactome)
GABAB receptorR-HSA-420688 (Reactome)
GABAR-HSA-420688 (Reactome)
GABR heteropentamers:GABA:NPTNArrowR-HSA-8856398 (Reactome)
GABR heteropentamers:GABAR-HSA-8856398 (Reactome)
GABR heteropentamers:GABAmim-catalysisR-HSA-975340 (Reactome)
GABRR pentamer:GABAmim-catalysisR-HSA-975449 (Reactome)
K+ArrowR-HSA-1013020 (Reactome)
K+R-HSA-1013020 (Reactome)
NPTNR-HSA-8856398 (Reactome)
PiArrowR-HSA-170666 (Reactome)
PiArrowR-HSA-170686 (Reactome)
R-HSA-1013020 (Reactome) Binding of G beta gamma activates the GIRK/Kir3 channels that allow the efflux of K+ out of the cell resulting in a hyperpolarized membrane potential. This negative membrane potential prevents the activation of voltage dependent Ca2+ channels.
R-HSA-170666 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-170671 (Reactome) The chronic activation of mu-opioid receptors, which, when coupled to pertussis toxin-sensitive Galpha-i/o proteins, inhibit adenylyl cyclase (AC).
R-HSA-170674 (Reactome) Once the intrinsic GTPase hydrolyzes GTP to GDP, Galpha-i dissociates from adenylate cyclase, allowing it to re-associate with G-beta-gamma and starting a new cycle.
R-HSA-170686 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-392206 (Reactome) G-proteins in the Gi class inhibit adenylate cyclase activity, decreasing the production of cAMP from ATP, which has many consequences but classically results in decreased activity of Protein Kinase A (PKA). cAMP also activates the cyclic nucleotide-gated ion channels, a process that is particularly important in olfactory cells.
R-HSA-420688 (Reactome) Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system. GABA exerts its effects through two ligand-gated channels and a the GPCR GABAB (Kaupmann K et al, 1998), which acts through G proteins to regulate potassium and calcium channels. GABAB can only bind GABA once it forms a heterodimer composed of the GABABR1 and GABABR2 receptors (White JH et al, 1998). The effects of this dimer are mediated by coupling to the G protein alpha i subunit, which inhibits adenylyl cyclase (Odagaki & Koyama 2001).
R-HSA-8856398 (Reactome) Neuroplastin (NPTN) is a glycoprotein that belongs to the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs). Together with basigin/CD147 and embigin, NPTN comprises the CD147 family (Iacono et al. 2007).

NPTN isoform p65 binds GABAA receptor subunits, co-localizing with alpha1 and alpha2, but not alpha3 subunits at GABAergic synapses and alpha5 subunits at extrasynaptic sites in cultures (Sarto-Jackson et al. 2012). GABAA receptors containing alpha1, 2 or 3 subunits are localized mainly at synaptic sites and interact with the scaffolding protein Gephyrin (GPHN), which anchors the receptor to the underlying postsynaptic complex and prevents their lateral diffusion (Kneussel & Loebrich 2007, Tretter et al. 2012). Receptors containing the alpha5 subunit are mainly extrasynaptic and link to the actin cytoskeleton via Radixin (Loebrich et al. 2006). NPTN p65 co-localization can be at several synaptic sites along the same dendrite, while absent from others. NPTN p65 shRNA caused diffuse alpha2 subunit staining which did not co-localize with vesicular inhibitory aa transporter, a presynaptic marker of GABAergic synapses (Sarto-Jackson et al. 2012). This suggests a functional role for NPTN p65 in regulating the composition and localization of GABAA receptors (Beesley et al. 2014). The absence of NPTN p65 causes early-onset sensorineural hearing loss and prevents normal synaptogenesis in cochleal inner hair cells (IHCs) (Carrott et al. 2016).
R-HSA-975340 (Reactome) 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.
R-HSA-975449 (Reactome) The GABA(A)-rho receptor (GABRR) is expressed in many areas of the brain, but in contrast to other GABA(A) receptors, has especially high expression in the retina. It is functional as a homopentamer and is permeable to chloride ions when GABA binds to it (Cutting et al. 1991, Cutting et al. 1992, Bailey et al. 1990).
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