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Gene Review

Cryge  -  crystallin, gamma E

Rattus norvegicus

Synonyms: Cryg5, Gamma-2, Gamma-E-crystallin, Gamma-crystallin 3-1, Gamma-crystallin E, ...
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Disease relevance of Cryge

  • Nephritogenic doses of both the noncomplement-fixing F(ab')2 portion and the gamma 2 subclass of anti-Fx1A IgG produced subepithelial deposits of immunoglobulin without C3, but proteinuria did not occur despite glomerular deposition of up to 70 microgram/2 kidneys of gamma 2 [1].
  • 5. Coupling to the alpha 2-adrenergic receptor was reconstituted in neurons expressing pertussis toxin (PTX)-insensitive G alpha(oA) and either tagged or untagged G beta 1 gamma 2 subunits [2].
  • These changes were selective to these alpha isoforms as neither beta 2 nor gamma 2 mRNA changed following seizures and occurred only in thalamic relay nuclei but not in hippocampus, a structure from which absence seizures do not evolve [3].
  • The distribution of GABAA receptor gamma 1 and gamma 2 subunits in the rat vestibular ganglion cells and end-organs was examined by using immunohistochemical techniques [4].
  • The PP1 gamma 2 protein was undetectable in both liver and hepatomas [5].

High impact information on Cryge

  • In consequence, alpha 6(Q100)beta 2 gamma 2 receptors show diazepam-mediated potentiation of GABA-activated currents and diazepam-sensitive binding of [3H]Ro15-4513 [6].
  • Rat wild-type or mutated alpha 1-, beta 2- and gamma 2-subunits (designated alpha, beta and gamma) were coexpressed in Xenopus oocytes and examined electrophysiologically [7].
  • We show that recombinant receptors composed of alpha 6, beta 2 and gamma 2 subunits bind with high affinity to the GABA agonist [3H]muscimol and the benzodiazepine [3H]Ro15-4513 but not the other benzodiazepines or beta-carboniles [8].
  • In view of these data and of previous results, we conclude that the galanin receptors in GH3 and in RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2 gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently [9].
  • The amounts of mRNAs encoding alpha 1, alpha 6, beta 2, beta 3, gamma 2, and delta subunits of gamma-aminobutyrate type A (GABAA) receptors and the gold immunolabeling density of their translation products were monitored during the growth of neonatal rat granule cells in primary culture [10].

Chemical compound and disease context of Cryge


Biological context of Cryge


Anatomical context of Cryge

  • Three native forms of PP1 gamma 2 were detected in a crude fraction of rat testis by electrophoresis in a nondenaturing polyacrylamide gel [11].
  • Mapping subunit gene expression by in situ hybridization histochemistry suggests that the alpha 1-, beta 1-, and gamma 2-subunits are likely receptor constituents in some neuronal populations, e.g., mitral cells of the olfactory bulb, pyramidal cells of the hippocampus, and granule cells of the dentate gyrus and cerebellum [13].
  • The results reveal a widespread expression of the subunits, alpha 3, beta 2,3, and gamma 2 in the spinal cord, whereas the three other alpha subunits displayed a more restricted, lamina-specific distribution [15].
  • The medial septum and globus pallidus were regions expressing few subunits in both early postnatal and adult stages, allowing clear developmental combinatorial changes to be inferred (alpha 2/alpha 3 beta 2 gamma 2 to alpha 1 beta 2 gamma 2, alpha 2/alpha 3 beta 2 gamma 1 to alpha 1 beta 2 gamma 1/gamma 2, respectively) [16].
  • Certain GABAA transcripts were also detected in germinal zones (e.g., beta 1, beta 3, gamma 1) and in embryonic peripheral tissues such as dorsal root ganglia (e.g., alpha 2, alpha 3, beta 3, gamma 2) and intestine (gamma 3) [16].

Associations of Cryge with chemical compounds

  • We purified a major native form of PP1 gamma 2 to homogeneity by successive column chromatography on Mono Q-Sepharose, EAH-agarose, protamine-agarose, and G3000SW and by electrophoresis in a nondenaturing polyacrylamide gel [11].
  • PP1 gamma 2, a testis-specific protein-serine/threonine-phosphatase type 1 catalytic subunit, is associated with a protein having high sequence homology with the 78-kDa glucose-regulated protein, a member of the 70-kDa heat shock protein family [11].
  • No cross-reactivity with the GABAA receptor subunits alpha 1-3, beta 1-3, gamma 2, delta or with the glycine receptor subunits alpha 1 and beta could be detected [17].
  • We mutated, one at a time, four consecutive residues (268-271) in the M2 membrane-spanning segment of the rat GABAA receptor alpha 1 subunit to cysteine and expressed the mutant alpha 1 subunits, together with either the beta 1 subunit or the beta 1 and gamma 2 subunits, in Xenopus oocytes [18].
  • GABARAP is localized on intracellular membranes such as the trans-Golgi network, binds to the gamma 2 subunit of GABA(A) receptors and interacts with microtubules and the N-ethylmaleimide-sensitive factor [19].

Physical interactions of Cryge

  • Brain regions with relatively high densities of alpha 1, beta 2 and gamma 2 subunits of GABAA and [3H]zolpidem binding included olfactory bulb, medial septum, ventral pallidum, diagonal band, inferior colliculus, substantia nigra pars reticulata and specific layers of the cortex [20].

Regulatory relationships of Cryge

  • In cultured noradrenergic neurons from the rat locus coeruleus, application of recombinant G protein beta 1 gamma 2 subunits (30 nM) to the cytoplasmic side induced single channel activity similar to the somatostatin-induced single channel activity of G protein-coupled inward rectifier potassium channels (Kir (G)) [21].
  • This study shows that only the gamma 2 subunit of the GABAA receptor gamma subunit family is expressed by hypothalamic oxytocin and vasopressin neurones [22].

Other interactions of Cryge

  • Messenger RNA levels for the N-methyl-D-aspartate receptor subunit, NR1; the non-N-methyl-D-aspartate receptor subunits, glutamate receptors 3 and 4; the high-affinity kainate receptor subunits 1 and 2; and the GABAA receptor subunits, alpha 2, beta 2, gamma 2 were unchanged [23].
  • In addition to coimmunoprecipitating with Gi alpha and G beta, brain SRIF receptors coimmunoprecipitated the G protein gamma subunits, G gamma 2 and G gamma 3 [24].
  • 7. In summary, the attachment of GFP mutants to the N-terminus of G beta 1 or G gamma 2 does not qualitatively impair their ability to form a heterotrimer, modulate effectors (N-type Ca(2+) and GIRK channels), or couple to receptors [2].
  • The localization of GABAA receptor gamma 1 and gamma 2 subunits and the AMPA-type glutamate receptor subunits GluR1 and GluR2/3 were identified in the caudal trigeminal spinal tract nucleus (TNC) by immunohistochemistry using specific antibodies [25].
  • Most of the neurons labeled by retrograde tracing also showed gamma 1- and gamma 2-like immunoreactivity, while many of the neurons containing FG lacked GluR1- and GluR2/3-like immunoreactivity [25].

Analytical, diagnostic and therapeutic context of Cryge

  • To identify receptor subtypes in situ, the most prevalent subunits were visualized by double and triple immunofluorescence staining in rat brain, using polyclonal antibodies to the alpha 1, alpha 3, and gamma 2 subunits and a monoclonal antibody to locate both the beta 2 and the beta 3 subunit [26].
  • This study has used in situ hybridization techniques to examine whether the content of alpha 1, alpha 2, beta 2, gamma 2 GABAA receptor subunit mRNAs expressed by these cells fluctuates over this period [14].
  • Immunoprecipitation with both antisera identified the gamma 2-subunit immunoreactivity in 40 and 50% of the native GABAA receptors purified from bovine and rat brains, respectively [27].
  • Northern blot analysis revealed the presence of mRNAs encoding alpha 1 and gamma 2 receptor subunits [28].
  • In situ hybridization studies demonstrated that mRNA levels for GABAA receptor alpha 1, alpha 2, beta 2, and gamma 2 subunits were altered in the hippocampus of female rats by adrenalectomy [29].


  1. A new role for complement in experimental membranous nephropathy in rats. Salant, D.J., Belok, S., Madaio, M.P., Couser, W.G. J. Clin. Invest. (1980) [Pubmed]
  2. Functional expression and FRET analysis of green fluorescent proteins fused to G-protein subunits in rat sympathetic neurons. Ruiz-Velasco, V., Ikeda, S.R. J. Physiol. (Lond.) (2001) [Pubmed]
  3. Alterations in GABAA receptor alpha 1 and alpha 4 subunit mRNA levels in thalamic relay nuclei following absence-like seizures in rats. Banerjee, P.K., Tillakaratne, N.J., Brailowsky, S., Olsen, R.W., Tobin, A.J., Snead, O.C. Exp. Neurol. (1998) [Pubmed]
  4. Expression of GABAA receptor gamma 1 and gamma 2 subunits in the peripheral vestibular system of the rat. Kitahara, T., Takeda, N., Ohno, K., Araki, T., Kubo, T., Kiyama, H. Brain Res. (1994) [Pubmed]
  5. Selective increases in isoform PP1 alpha of type-1 protein phosphatase in ascites hepatoma cells. Takizawa, N., Mizuno, Y., Saadat, M., Kikuchi, K. Jpn. J. Cancer Res. (1994) [Pubmed]
  6. 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]
  7. GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital. Amin, J., Weiss, D.S. Nature (1993) [Pubmed]
  8. Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Lüddens, H., Pritchett, D.B., Köhler, M., Killisch, I., Keinänen, K., Monyer, H., Sprengel, R., Seeburg, P.H. Nature (1990) [Pubmed]
  9. Subunit composition of G(o) proteins functionally coupling galanin receptors to voltage-gated calcium channels. Kalkbrenner, F., Degtiar, V.E., Schenker, M., Brendel, S., Zobel, A., Heschler, J., Wittig, B., Schultz, G. EMBO J. (1995) [Pubmed]
  10. Changes in gamma-aminobutyrate type A receptor subunit mRNAs, translation product expression, and receptor function during neuronal maturation in vitro. Zheng, T.M., Zhu, W.J., Puia, G., Vicini, S., Grayson, D.R., Costa, E., Caruncho, H.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. PP1 gamma 2, a testis-specific protein-serine/threonine-phosphatase type 1 catalytic subunit, is associated with a protein having high sequence homology with the 78-kDa glucose-regulated protein, a member of the 70-kDa heat shock protein family. Chun, Y.S., Shima, H., Nagasaki, K., Sugimura, T., Nagao, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  12. Fc epsilon R1-mediated tyrosine phosphorylation of multiple proteins, including phospholipase C gamma 1 and the receptor beta gamma 2 complex, in RBL-2H3 rat basophilic leukemia cells. Li, W., Deanin, G.G., Margolis, B., Schlessinger, J., Oliver, J.M. Mol. Cell. Biol. (1992) [Pubmed]
  13. Functional characteristics and sites of gene expression of the alpha 1, beta 1, gamma 2-isoform of the rat GABAA receptor. Malherbe, P., Sigel, E., Baur, R., Persohn, E., Richards, J.G., Mohler, H. J. Neurosci. (1990) [Pubmed]
  14. Plasticity in GABAA receptor subunit mRNA expression by hypothalamic magnocellular neurons in the adult rat. Fénelon, V.S., Herbison, A.E. J. Neurosci. (1996) [Pubmed]
  15. Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord: an immunohistochemical study. Bohlhalter, S., Weinmann, O., Mohler, H., Fritschy, J.M. J. Neurosci. (1996) [Pubmed]
  16. The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. Laurie, D.J., Wisden, W., Seeburg, P.H. J. Neurosci. (1992) [Pubmed]
  17. Immunocytochemical localization of the GABAc receptor rho subunits in the mammalian retina. Enz, R., Brandstätter, J.H., Wässle, H., Bormann, J. J. Neurosci. (1996) [Pubmed]
  18. Amino acids lining the channel of the gamma-aminobutyric acid type A receptor identified by cysteine substitution. Xu, M., Akabas, M.H. J. Biol. Chem. (1993) [Pubmed]
  19. Crystal structure of the GABA(A)-receptor-associated protein, GABARAP. Bavro, V.N., Sola, M., Bracher, A., Kneussel, M., Betz, H., Weissenhorn, W. EMBO Rep. (2002) [Pubmed]
  20. Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the alpha 1, beta 2 and gamma 2 subunits of GABAA receptors in rat brain. Duncan, G.E., Breese, G.R., Criswell, H.E., McCown, T.J., Herbert, J.S., Devaud, L.L., Morrow, A.L. Neuroscience (1995) [Pubmed]
  21. Activation of G protein-coupled inward rectifier K+ channels in brain neurons requires association of G protein beta gamma subunits with cell membrane. Nakajima, Y., Nakajima, S., Kozasa, T. FEBS Lett. (1996) [Pubmed]
  22. Characterisation of GABAA receptor gamma subunit expression by magnocellular neurones in rat hypothalamus. Fenelon, V.S., Herbison, A.E. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  23. Alterations in glutamate but not GABAA receptor subunit expression as a consequence of epileptiform activity in vitro. Gerfin-Moser, A., Grogg, F., Rietschin, L., Thompson, S.M., Streit, P. Neuroscience (1995) [Pubmed]
  24. Identification of the subunits of GTP-binding proteins coupled to somatostatin receptors. Law, S.F., Manning, D., Reisine, T. J. Biol. Chem. (1991) [Pubmed]
  25. Expression of glutamate (AMPA type) and gamma-aminobutyric acid (GABA)A receptors in the rat caudal trigeminal spinal nucleus. Kondo, E., Kiyama, H., Yamano, M., Shida, T., Ueda, Y., Tohyama, M. Neurosci. Lett. (1995) [Pubmed]
  26. Five subtypes of type A gamma-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies. Fritschy, J.M., Benke, D., Mertens, S., Oertel, W.H., Bachi, T., Möhler, H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  27. GABAA receptors display association of gamma 2-subunit with alpha 1- and beta 2/3-subunits. Benke, D., Mertens, S., Trzeciak, A., Gillessen, D., Mohler, H. J. Biol. Chem. (1991) [Pubmed]
  28. Stable expression of type I gamma-aminobutyric acidA/benzodiazepine receptors in a transfected cell line. Wong, G., Sei, Y., Skolnick, P. Mol. Pharmacol. (1992) [Pubmed]
  29. Adrenalectomy selectively regulates GABAA receptor subunit expression in the hippocampus. Orchinik, M., Weiland, N.G., McEwen, B.S. Mol. Cell. Neurosci. (1994) [Pubmed]
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