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Gene Review

Gabra6  -  gamma-aminobutyric acid (GABA) A receptor,...

Mus musculus

Synonyms: GABA(A) receptor subunit alpha-6, GABA-ARalpha6, Gabra-6, Gamma-aminobutyric acid receptor subunit alpha-6, alpha6
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Disease relevance of Gabra6


Psychiatry related information on Gabra6

  • Imidazenil, which fails to modulate alpha1-, alpha4-, and alpha6-containing GABA(A)-Rs but is a selective positive allosteric modulator of alpha5-containing GABA(A)-Rs, also increases locomotor activity in SI mice [6].

High impact information on Gabra6


Chemical compound and disease context of Gabra6


Biological context of Gabra6


Anatomical context of Gabra6


Associations of Gabra6 with chemical compounds

  • Acute ethanol injection resulted in increased expression of alpha 1 and beta 3 mRNAs, whereas levels of alpha 6, beta 2, and gamma 2 mRNAs remained stable [20].
  • Of the 15 genes known to code for GABA receptor subunits in mammals we have examined the expression of 12 in the SCN, neglecting only the alpha 6, gamma 3, and rho 2 subunits [21].
  • Similarly, the alpha6 subunit does not seem to be involved in the behavioral responses to general anesthetics or pentobarbital [18].
  • A critical determinant for diazepam insensitivity of this 'wild-type' cerebellar GABAA receptor is an arginine residue in alpha 6 position 100, where other alpha subunits carry a histidine [22].
  • Here we report that the alpha 6 gene of ANT rats is expressed at wild-type levels but carries a point mutation generating an arginine-to-glutamine substitution at position 100 [22].

Physical interactions of Gabra6


Enzymatic interactions of Gabra6


Co-localisations of Gabra6


Regulatory relationships of Gabra6

  • Keratin 8 and gamma-glutamyltranspeptidase were expressed only in alpha 6 beta 4 positive cells [29].
  • PECAM-1 (CD31) homophilic interaction up-regulates alpha6beta1 on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane [30].
  • Overall, the reported findings indicate that alpha 6 beta 4 integrin promotes growth arrest and differentiation by modulating Abl kinases and p73 protein pathway(s) [31].
  • By contrast, C-23 cells expressed low or undetectable levels of alpha1, alpha2, and alpha6 but had up-regulated levels of alpha7 [32].

Other interactions of Gabra6

  • Here we show that this tonic conductance is absent in granule cells that lack the alpha6 and delta-subunits of the GABAA receptor [33].
  • Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells [13].
  • Mouse cerebellar granule cell differentiation: electrical activity regulates the GABAA receptor alpha 6 subunit gene [12].
  • Electron microscopic immunogold labeling shows that most Thy1-derived alpha6 immunoreactivity is in the extrasynaptic plasma membrane of dendrites and spines in both layer V isocortical and CA1pyramidal cells [34].
  • Intravenous injection of anti-integrin alpha6 antibodies, in contrast to antibodies against alpha4 integrin, did not mobilize progenitors or enhance cytokine-induced mobilization by G-CSF [35].
  • PCR analysis identified a dramatic reduction in the steady-state level of alpha6 mRNA, compatible with alpha6 being the primary target of the stargazer mutation-mediated GABA(A) receptor abnormalities [36].

Analytical, diagnostic and therapeutic context of Gabra6


  1. Cerebellar granule-cell-specific GABAA receptors attenuate benzodiazepine-induced ataxia: evidence from alpha 6-subunit-deficient mice. Korpi, E.R., Koikkalainen, P., Vekovischeva, O.Y., Mäkelä, R., Kleinz, R., Uusi-Oukari, M., Wisden, W. Eur. J. Neurosci. (1999) [Pubmed]
  2. Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice. Georges-Labouesse, E., Messaddeq, N., Yehia, G., Cadalbert, L., Dierich, A., Le Meur, M. Nat. Genet. (1996) [Pubmed]
  3. The major laminin receptor of mouse embryonic stem cells is a novel isoform of the alpha 6 beta 1 integrin. Cooper, H.M., Tamura, R.N., Quaranta, V. J. Cell Biol. (1991) [Pubmed]
  4. Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival. Dowling, J., Yu, Q.C., Fuchs, E. J. Cell Biol. (1996) [Pubmed]
  5. A splice variant of alpha 6 integrin is associated with malignant conversion in mouse skin tumorigenesis. Tennenbaum, T., Belanger, A.J., Glick, A.B., Tamura, R., Quaranta, V., Yuspa, S.H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation. Pinna, G., Agis-Balboa, R.C., Zhubi, A., Matsumoto, K., Grayson, D.R., Costa, E., Guidotti, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice. van der Neut, R., Krimpenfort, P., Calafat, J., Niessen, C.M., Sonnenberg, A. Nat. Genet. (1996) [Pubmed]
  8. Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Almeida, E.A., Huovila, A.P., Sutherland, A.E., Stephens, L.E., Calarco, P.G., Shaw, L.M., Mercurio, A.M., Sonnenberg, A., Primakoff, P., Myles, D.G., White, J.M. Cell (1995) [Pubmed]
  9. Temozolomide reduces the metastatic potential of Lewis lung carcinoma (3LL) in mice: role of alpha-6 integrin phosphorylation. Tentori, L., Leonetti, C., Aquino, A. Eur. J. Cancer (1995) [Pubmed]
  10. Changes in the expression of integrins and basement membrane proteins in benign mucous membrane pemphigoid. Jones, J., Downer, C.S., Speight, P.M. Oral diseases. (1995) [Pubmed]
  11. Suppression of mouse melanoma metastasis by EA-1, a monoclonal antibody specific for alpha 6 integrins. Ruiz, P., Dunon, D., Sonnenberg, A., Imhof, B.A. Cell Adhes. Commun. (1993) [Pubmed]
  12. Mouse cerebellar granule cell differentiation: electrical activity regulates the GABAA receptor alpha 6 subunit gene. Mellor, J.R., Merlo, D., Jones, A., Wisden, W., Randall, A.D. J. Neurosci. (1998) [Pubmed]
  13. Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression. Jones, A., Korpi, E.R., McKernan, R.M., Pelz, R., Nusser, Z., Mäkelä, R., Mellor, J.R., Pollard, S., Bahn, S., Stephenson, F.A., Randall, A.D., Sieghart, W., Somogyi, P., Smith, A.J., Wisden, W. J. Neurosci. (1997) [Pubmed]
  14. Directing gene expression to cerebellar granule cells using gamma-aminobutyric acid type A receptor alpha6 subunit transgenes. Bahn, S., Jones, A., Wisden, W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  15. Characterization of a cerebellar granule cell-specific gene encoding the gamma-aminobutyric acid type A receptor alpha 6 subunit. Jones, A., Bahn, S., Grant, A.L., Köhler, M., Wisden, W. J. Neurochem. (1996) [Pubmed]
  16. Alterations in the expression of GABAA receptor subunits in cerebellar granule cells after the disruption of the alpha6 subunit gene. Nusser, Z., Ahmad, Z., Tretter, V., Fuchs, K., Wisden, W., Sieghart, W., Somogyi, P. Eur. J. Neurosci. (1999) [Pubmed]
  17. GABAA receptor function and regional analysis of subunit mRNAs in long-sleep and short-sleep mouse brain. Zahniser, N.R., Buck, K.J., Curella, P., McQuilkin, S.J., Wilson-Shaw, D., Miller, C.L., Klein, R.L., Heidenreich, K.A., Keir, W.J., Sikela, J.M. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  18. Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. Homanics, G.E., Ferguson, C., Quinlan, J.J., Daggett, J., Snyder, K., Lagenaur, C., Mi, Z.P., Wang, X.H., Grayson, D.R., Firestone, L.L. Mol. Pharmacol. (1997) [Pubmed]
  19. GABAA/benzodiazepine receptor alpha 6 subunit mRNA in granule cells of the cerebellar cortex and cochlear nuclei: expression in developing and mutant mice. Varecka, L., Wu, C.H., Rotter, A., Frostholm, A. J. Comp. Neurol. (1994) [Pubmed]
  20. Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand binding sites in mouse cerebellar neurons following in vivo ethanol administration: an autoradiographic analysis. Wu, C.H., Frostholm, A., De Blas, A.L., Rotter, A. J. Neurochem. (1995) [Pubmed]
  21. GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus and other brain regions. O'Hara, B.F., Andretic, R., Heller, H.C., Carter, D.B., Kilduff, T.S. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  22. Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Korpi, E.R., Kleingoor, C., Kettenmann, H., Seeburg, P.H. Nature (1993) [Pubmed]
  23. Analysis of integrin receptors for laminin and type IV collagen on metastatic B16 melanoma cells. Ramos, D.M., Berston, E.D., Kramer, R.H. Cancer Res. (1990) [Pubmed]
  24. Evidence that distinct states of the integrin alpha6beta1 interact with laminin and an ADAM. Chen, M.S., Almeida, E.A., Huovila, A.P., Takahashi, Y., Shaw, L.M., Mercurio, A.M., White, J.M. J. Cell Biol. (1999) [Pubmed]
  25. Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the alpha6 subunit. Parker, S.L., Fu, Y., McAllen, K., Luo, J., McIntosh, J.M., Lindstrom, J.M., Sharp, B.M. Mol. Pharmacol. (2004) [Pubmed]
  26. Mediation of sperm-egg fusion: evidence that mouse egg alpha6beta1 integrin is the receptor for sperm fertilinbeta. Chen, H., Sampson, N.S. Chem. Biol. (1999) [Pubmed]
  27. Regulation of alpha 6 beta 1 integrin laminin receptor function by the cytoplasmic domain of the alpha 6 subunit. Shaw, L.M., Mercurio, A.M. J. Cell Biol. (1993) [Pubmed]
  28. Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes. Stepp, M.A., Spurr-Michaud, S., Tisdale, A., Elwell, J., Gipson, I.K. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  29. The suprabasal expression of alpha 6 beta 4 integrin is associated with a high risk for malignant progression in mouse skin carcinogenesis. Tennenbaum, T., Weiner, A.K., Belanger, A.J., Glick, A.B., Hennings, H., Yuspa, S.H. Cancer Res. (1993) [Pubmed]
  30. PECAM-1 (CD31) homophilic interaction up-regulates alpha6beta1 on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane. Dangerfield, J., Larbi, K.Y., Huang, M.T., Dewar, A., Nourshargh, S. J. Exp. Med. (2002) [Pubmed]
  31. Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells. Morena, A., Riccioni, S., Marchetti, A., Polcini, A.T., Mercurio, A.M., Blandino, G., Sacchi, A., Falcioni, R. Blood (2002) [Pubmed]
  32. Expression of the alpha7beta1 laminin receptor suppresses melanoma growth and metastatic potential. Ziober, B.L., Chen, Y.Q., Ramos, D.M., Waleh, N., Kramer, R.H. Cell Growth Differ. (1999) [Pubmed]
  33. Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Brickley, S.G., Revilla, V., Cull-Candy, S.G., Wisden, W., Farrant, M. Nature (2001) [Pubmed]
  34. Ectopic expression of the GABA(A) receptor alpha6 subunit in hippocampal pyramidal neurons produces extrasynaptic receptors and an increased tonic inhibition. Wisden, W., Cope, D., Klausberger, T., Hauer, B., Sinkkonen, S.T., Tretter, V., Lujan, R., Jones, A., Korpi, E.R., Mody, I., Sieghart, W., Somogyi, P. Neuropharmacology (2002) [Pubmed]
  35. Contribution of alpha6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with alpha4 integrins. Qian, H., Tryggvason, K., Jacobsen, S.E., Ekblom, M. Blood (2006) [Pubmed]
  36. GABAA alpha6-containing receptors are selectively compromised in cerebellar granule cells of the ataxic mouse, stargazer. Payne, H.L., Connelly, W.M., Ives, J.H., Lehner, R., Furtmuller, B., Sieghart, W., Tiwari, P., Lucocq, J.M., Lees, G., Thompson, C.L. J. Biol. Chem. (2007) [Pubmed]
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