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Gene Review

RYR3  -  ryanodine receptor 3

Homo sapiens

Synonyms: Brain ryanodine receptor-calcium release channel, Brain-type ryanodine receptor, HBRR, RYR-3, RyR3, ...
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Disease relevance of RYR3


High impact information on RYR3

  • The observed physiological and behavioral effects implicate RyR3-mediated Ca(2+) release in the intracellular processes underlying spatial learning and hippocampal synaptic plasticity [6].
  • Deletion of the ryanodine receptor type 3 (RyR3) results in specific changes in hippocampal synaptic plasticity, without affecting hippocampal morphology, basal synaptic transmission or presynaptic function [6].
  • The expression of RyR3 in skeletal muscles was studied in mice from late fetal stages to adult life [3].
  • RyR3 was found to be expressed widely in murine skeletal muscles during the post-natal phase of muscle development, but was not detectable in muscles of adult mice, with the exception of the diaphragm and soleus muscles [3].
  • In the testis, expression of RyR1 and RyR3 was detected in germ cells [7].

Biological context of RYR3


Anatomical context of RYR3

  • In untreated Jurkat T cells, 4CmC (>1 mM) had no effect on Ca(2+) release, whereas 4CmC (<400 microM) caused Ca(2+) release after the induction of RYR2 and RYR3 that occurred after treatment with stromal cell-derived factor 1, macrophage-inflammatory protein-1alpha, or TGF-beta [12].
  • Ribonuclease protection assays revealed that one of these splice variants, RyR3 (AS-8a), which lacks a 29-amino acid fragment (His(4406)-Lys(4434)) encompassing a predicted transmembrane helix, was highly expressed in smooth muscle tissues, but not in skeletal muscle, the heart, or the brain [10].
  • CONCLUSIONS: Our findings suggest that, in addition to InsP(3) mediated Ca(2+) release, Ca(2+) release from ryanodine-sensitive stores mediated by RyR3 and Ca(2+) entry through TRP1 might represent important components of endothelial Ca(2+) signaling in situ and thereby of endothelial function in intact human blood vessels [13].
  • Vincenzo Sorrentino and Pompeo Volpe review some recent developments: the ryanodine receptor channels have now been found to be expressed in the central nervous system, and the cloning of a third ryanodine receptor gene (RYR3) has revealed that this new isoform is widely expressed in several tissues and cells [14].
  • In the uterus and vas deferens, expression of RyR3 was localized to the smooth muscle component of these organs [7].

Associations of RYR3 with chemical compounds

  • Our results thus indicate that both the RYR1 and the RYR3, but not the RYR2, may be targets for dantrolene inhibition in vivo [15].
  • It is well known that the type 3 Ca(2+) release channel (ryanodine receptor, RyR3) exhibits strikingly different pharmacological and functional properties depending on the tissues in which it resides [10].
  • Although the RyR3 (AS-8a) splice variant did not form a functional Ca(2+) release channel when expressed alone in HEK293 cells, it was able to form functional heteromeric channels with reduced caffeine sensitivity when co-expressed with the wild type RyR3 [10].
  • RyR3 in the presence of reduced glutathione binds CaM with 10-15-fold higher affinity, at low and high Ca(2+) concentrations, compared to in the presence of oxidized glutathione [11].
  • Purified recombinant RyR3 and GST-RyR3 proteins exhibited high-affinity [(3)H]ryanodine binding that was sensitive to activation by Ca(2+) and caffeine and to inhibition by Mg(2+) [16].

Regulatory relationships of RYR3

  • Interestingly, this RyR3 splice variant was also able to form heteromeric channels with and suppress the activity of the type 2 ryanodine receptor (RyR2) [10].
  • At low Ca(2+) concentrations (<1 microM), CaM activates RyR1 and RyR3 and inhibits RyR2 [11].

Other interactions of RYR3

  • Co-expression of a ryanodine binding deficient mutant of RyR2, RyR2 (I4827T), with RyR3 (wt) restored [(3)H]ryanodine binding to the mutant [17].
  • CKTFS1B1 was localized on human chromosome 15q13--> q15 by somatic cell hybrid analysis and, more precisely, using radiation hybrids, to a region of markers linked to SGNE1, secretory granule neuroendocrine protein 1 and RYR3, the ryanodyne receptor 3 [18].
  • Permeabilized RyR3-transduced myotubes exhibited similar punctate peripheral RyR3 protein immunohistochemical patterns as myotubes fixed before permeabilization indicating that permeabilization did not affect the structural organization of the triad [19].

Analytical, diagnostic and therapeutic context of RYR3


  1. Mutation analysis of the ryanodine receptor gene isoform 3 (RYR3) in recurrent neuroleptic malignant syndrome. Dettling, M., Sander, T., Weber, M., Steinlein, O.K. Journal of clinical psychopharmacology. (2004) [Pubmed]
  2. Expression levels of RyR1 and RyR3 control resting free Ca2+ in skeletal muscle. Perez, C.F., López, J.R., Allen, P.D. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  3. Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles. Bertocchini, F., Ovitt, C.E., Conti, A., Barone, V., Schöler, H.R., Bottinelli, R., Reggiani, C., Sorrentino, V. EMBO J. (1997) [Pubmed]
  4. Type-3 ryanodine receptors mediate hypoxia-, but not neurotransmitter-induced calcium release and contraction in pulmonary artery smooth muscle cells. Zheng, Y.M., Wang, Q.S., Rathore, R., Zhang, W.H., Mazurkiewicz, J.E., Sorrentino, V., Singer, H.A., Kotlikoff, M.I., Wang, Y.X. J. Gen. Physiol. (2005) [Pubmed]
  5. Molecular cloning and characterization of a human brain ryanodine receptor. Nakashima, Y., Nishimura, S., Maeda, A., Barsoumian, E.L., Hakamata, Y., Nakai, J., Allen, P.D., Imoto, K., Kita, T. FEBS Lett. (1997) [Pubmed]
  6. Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning. Balschun, D., Wolfer, D.P., Bertocchini, F., Barone, V., Conti, A., Zuschratter, W., Missiaen, L., Lipp, H.P., Frey, J.U., Sorrentino, V. EMBO J. (1999) [Pubmed]
  7. The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. Giannini, G., Conti, A., Mammarella, S., Scrobogna, M., Sorrentino, V. J. Cell Biol. (1995) [Pubmed]
  8. Localization of a novel ryanodine receptor gene (RYR3) to human chromosome 15q14-q15 by in situ hybridization. Sorrentino, V., Giannini, G., Malzac, P., Mattei, M.G. Genomics (1993) [Pubmed]
  9. cDNA cloning and sequencing of the human ryanodine receptor type 3 (RYR3) reveals a novel alternative splice site in the RYR3 gene. Leeb, T., Brenig, B. FEBS Lett. (1998) [Pubmed]
  10. Smooth muscle tissues express a major dominant negative splice variant of the type 3 Ca2+ release channel (ryanodine receptor). Jiang, D., Xiao, B., Li, X., Chen, S.R. J. Biol. Chem. (2003) [Pubmed]
  11. Calmodulin regulation and identification of calmodulin binding region of type-3 ryanodine receptor calcium release channel. Yamaguchi, N., Xu, L., Pasek, D.A., Evans, K.E., Chen, S.R., Meissner, G. Biochemistry (2005) [Pubmed]
  12. Expression of the ryanodine receptor isoforms in immune cells. Hosoi, E., Nishizaki, C., Gallagher, K.L., Wyre, H.W., Matsuo, Y., Sei, Y. J. Immunol. (2001) [Pubmed]
  13. Expression of ryanodine receptor type 3 and TRP channels in endothelial cells: comparison of in situ and cultured human endothelial cells. Köhler, R., Brakemeier, S., Kühn, M., Degenhardt, C., Buhr, H., Pries, A., Hoyer, J. Cardiovasc. Res. (2001) [Pubmed]
  14. Ryanodine receptors: how many, where and why? Sorrentino, V., Volpe, P. Trends Pharmacol. Sci. (1993) [Pubmed]
  15. Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity. Zhao, F., Li, P., Chen, S.R., Louis, C.F., Fruen, B.R. J. Biol. Chem. (2001) [Pubmed]
  16. Three-dimensional reconstruction of the recombinant type 3 ryanodine receptor and localization of its amino terminus. Liu, Z., Zhang, J., Sharma, M.R., Li, P., Chen, S.R., Wagenknecht, T. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  17. Isoform-dependent formation of heteromeric Ca2+ release channels (ryanodine receptors). Xiao, B., Masumiya, H., Jiang, D., Wang, R., Sei, Y., Zhang, L., Murayama, T., Ogawa, Y., Lai, F.A., Wagenknecht, T., Chen, S.R. J. Biol. Chem. (2002) [Pubmed]
  18. DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain. Topol, L.Z., Modi, W.S., Koochekpour, S., Blair, D.G. Cytogenet. Cell Genet. (2000) [Pubmed]
  19. Expression of ryanodine receptor RyR3 produces Ca2+ sparks in dyspedic myotubes. Ward, C.W., Schneider, M.F., Castillo, D., Protasi, F., Wang, Y., Chen, S.R., Allen, P.D. J. Physiol. (Lond.) (2000) [Pubmed]
  20. Characterization of the sarcoplasmic reticulum k(+) and Ca(2+)-release channel-ryanodine receptor-in human atrial cells. Côté, K., Proteau, S., Teijeira, J., Rousseau, E. J. Mol. Cell. Cardiol. (2000) [Pubmed]
  21. Functional characterization of the recombinant type 3 Ca2+ release channel (ryanodine receptor) expressed in HEK293 cells. Chen, S.R., Li, X., Ebisawa, K., Zhang, L. J. Biol. Chem. (1997) [Pubmed]
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