Biology:RYR1

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Generic protein structure example

Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is a protein found primarily in skeletal muscle. In humans, it is encoded by the RYR1 gene.[1][2]

Function

RYR1 functions as a calcium release channel in the sarcoplasmic reticulum, as well as a connection between the sarcoplasmic reticulum and the transverse tubule.[3] RYR1 is associated with the dihydropyridine receptor (L-type calcium channels) within the sarcolemma of the T-tubule, which opens in response to depolarization, and thus effectively means that the RYR1 channel opens in response to depolarization of the cell.

RYR1 plays a signaling role during embryonic skeletal myogenesis. A correlation exists between RYR1-mediated Ca2+ signaling and the expression of multiple molecules involved in key myogenic signaling pathways.[4] Of these, more than 10 differentially expressed genes belong to the Wnt family which are essential for differentiation. This coincides with the observation that without RYR1 present, muscle cells appear in smaller groups, are underdeveloped, and lack organization. Fiber type composition is also affected, with less type 1 muscle fibers when there are decreased amounts of RYR1.[5] These findings demonstrate RYR1 has a non-contractile role during muscle development.

RYR1 is mechanically linked to neuromuscular junctions for the calcium release-calcium induced biological process. While nerve-derived signals are required for acetylcholine receptor cluster distribution, there is evidence to suggest RYR1 activity is an important mediator in the formation and patterning of these receptors during embryological development.[6] The signals from the nerve and RYR1 activity appear to counterbalance each other. When RYR1 is eliminated, the acetylcholine receptor clusters appear in an abnormally narrow pattern, yet without signals from the nerve, the clusters are scattered and broad. Although their direct role is still unknown, RYR1 is required for proper distribution of acetylcholine receptor clusters.

Clinical significance

Mutations in the RYR1 gene are associated with malignant hyperthermia susceptibility, central core disease, minicore myopathy with external ophthalmoplegia and samaritan myopathy, a benign congenital myopathy.[7] Alternatively spliced transcripts encoding different isoforms have been demonstrated.[3] Dantrolene may be the only known drug that is effective during cases of malignant hyperthermia.[citation needed]

Interactions

RYR1 has been shown to interact with:

See also

References

  1. ↑ "Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia". Science 253 (5018): 448–51. July 1991. doi:10.1126/science.1862346. PMID 1862346. 
  2. ↑ "Central core disease is due to RYR1 mutations in more than 90% of patients". Brain 129 (Pt 6): 1470–80. June 2006. doi:10.1093/brain/awl077. PMID 16621918. 
  3. ↑ 3.0 3.1 "Entrez Gene: RYR1 ryanodine receptor 1 (skeletal)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6261. 
  4. ↑ "Corrigendum: Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca(2+) release channel". Scientific Reports 6: 24450. April 2016. doi:10.1038/srep24450. PMID 27102063. 
  5. ↑ "Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition". Pflügers Archiv 468 (2): 269–78. February 2016. doi:10.1007/s00424-015-1738-9. PMID 26438192. 
  6. ↑ "An explant muscle model to examine the refinement of the synaptic landscape". Journal of Neuroscience Methods 238: 95–104. December 2014. doi:10.1016/j.jneumeth.2014.09.013. PMID 25251554. 
  7. ↑ "Samaritan myopathy, an ultimately benign congenital myopathy, is caused by a RYR1 mutation". Acta Neuropathologica 124 (4): 575–81. October 2012. doi:10.1007/s00401-012-1007-3. PMID 22752422. 
  8. ↑ "Direct detection of calmodulin tuning by ryanodine receptor channel targets using a Ca2+-sensitive acrylodan-labeled calmodulin". Biochemistry 44 (1): 278–84. January 2005. doi:10.1021/bi048246u. PMID 15628869. 
  9. ↑ "FRET-based mapping of calmodulin bound to the RyR1 Ca2+ release channel". Proceedings of the National Academy of Sciences of the United States of America 106 (15): 6128–33. April 2009. doi:10.1073/pnas.0813010106. PMID 19332786. 
  10. ↑ "FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes". The Journal of Biological Chemistry 278 (25): 22600–8. June 2003. doi:10.1074/jbc.M205866200. PMID 12704193. 
  11. ↑ "Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor". The Biochemical Journal 354 (Pt 2): 413–22. March 2001. doi:10.1042/bj3540413. PMID 11171121. 
  12. ↑ "FKBP12 binding modulates ryanodine receptor channel gating". The Journal of Biological Chemistry 276 (20): 16931–5. May 2001. doi:10.1074/jbc.M100856200. PMID 11279144. 
  13. ↑ "Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling". Cell Calcium 34 (2): 177–84. August 2003. doi:10.1016/S0143-4160(03)00082-4. PMID 12810060. 
  14. ↑ 14.0 14.1 14.2 "Homer regulates gain of ryanodine receptor type 1 channel complex". The Journal of Biological Chemistry 277 (47): 44722–30. November 2002. doi:10.1074/jbc.M207675200. PMID 12223488. 
  15. ↑ "Negatively charged amino acids within the intraluminal loop of ryanodine receptor are involved in the interaction with triadin". The Journal of Biological Chemistry 279 (8): 6994–7000. February 2004. doi:10.1074/jbc.M312446200. PMID 14638677. 
  16. ↑ "Location of ryanodine receptor binding site on skeletal muscle triadin". Biochemistry 38 (1): 90–7. January 1999. doi:10.1021/bi981306+. PMID 9890886. 
  17. ↑ "Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum". The Journal of Biological Chemistry 270 (16): 9027–30. April 1995. doi:10.1074/jbc.270.16.9027. PMID 7721813. 
  18. ↑ "Functional interaction of the cytoplasmic domain of triadin with the skeletal ryanodine receptor". The Journal of Biological Chemistry 274 (18): 12278–83. April 1999. doi:10.1074/jbc.274.18.12278. PMID 10212196. 

Further reading

  • "Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders". Neuromuscular Disorders 15 (9–10): 577–87. October 2005. doi:10.1016/j.nmd.2005.06.008. PMID 16084090. 

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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