Ryanodine receptor 1

RYR1 functions as a calcium release channel in the sarcoplasmic reticulum, as well as a connection between the sarcoplasmic reticulum and the transverse tubule.{{cite web | title = Entrez Gene: RYR1 ryanodine receptor 1 (skeletal)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6261}} 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.{{cite journal | vauthors = Filipova D, Walter AM, Gaspar JA, Brunn A, Linde NF, Ardestani MA, Deckert M, Hescheler J, Pfitzer G, Sachinidis A, Papadopoulos S | title = Corrigendum: Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca(2+) release channel | journal = Scientific Reports | volume = 6 | pages = 24450 | date = April 2016 | pmid = 27102063 | doi = 10.1038/srep24450 | pmc=4840354| bibcode = 2016NatSR...624450F }} 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.{{cite journal | vauthors = Willemse H, Theodoratos A, Smith PN, Dulhunty AF | title = Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition | journal = Pflügers Archiv | volume = 468 | issue = 2 | pages = 269–78 | date = February 2016 | pmid = 26438192 | doi = 10.1007/s00424-015-1738-9 | s2cid = 5894066 }} 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.{{cite journal | vauthors = Hanson MG, Niswander LA | title = An explant muscle model to examine the refinement of the synaptic landscape | journal = Journal of Neuroscience Methods | volume = 238 | pages = 95–104 | date = December 2014 | pmid = 25251554 | doi = 10.1016/j.jneumeth.2014.09.013 | pmc=4252626}} 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.

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.{{cite journal | vauthors = Böhm J, Leshinsky-Silver E, Vassilopoulos S, Le Gras S, Lerman-Sagie T, Ginzberg M, Jost B, Lev D, Laporte J | title = Samaritan myopathy, an ultimately benign congenital myopathy, is caused by a RYR1 mutation | journal = Acta Neuropathologica | volume = 124 | issue = 4 | pages = 575–81 | date = October 2012 | pmid = 22752422 | doi = 10.1007/s00401-012-1007-3 | s2cid = 9014320 }} Alternatively spliced transcripts encoding different isoforms have been demonstrated. Dantrolene may be the only known drug that is effective during cases of malignant hyperthermia.{{citation needed|date=March 2015}}

RYR1 has been shown to interact with:

• calmodulin{{cite journal | vauthors = Fruen BR, Balog EM, Schafer J, Nitu FR, Thomas DD, Cornea RL | title = Direct detection of calmodulin tuning by ryanodine receptor channel targets using a Ca2+-sensitive acrylodan-labeled calmodulin | journal = Biochemistry | volume = 44 | issue = 1 | pages = 278–84 | date = January 2005 | pmid = 15628869 | doi = 10.1021/bi048246u | citeseerx = 10.1.1.578.9139 }}{{cite journal | vauthors = Cornea RL, Nitu F, Gruber S, Kohler K, Satzer M, Thomas DD, Fruen BR | title = FRET-based mapping of calmodulin bound to the RyR1 Ca2+ release channel | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 15 | pages = 6128–33 | date = April 2009 | pmid = 19332786 | pmc = 2662960 | doi = 10.1073/pnas.0813010106 | bibcode = 2009PNAS..106.6128C | doi-access = free }}
• FKBP1A{{cite journal | vauthors = Avila G, Lee EH, Perez CF, Allen PD, Dirksen RT | title = FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 25 | pages = 22600–8 | date = June 2003 | pmid = 12704193 | doi = 10.1074/jbc.M205866200 | doi-access = free }}{{cite journal | vauthors = Bultynck G, De Smet P, Rossi D, Callewaert G, Missiaen L, Sorrentino V, De Smedt H, Parys JB | title = 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 | journal = The Biochemical Journal | volume = 354 | issue = Pt 2 | pages = 413–22 | date = March 2001 | pmid = 11171121 | pmc = 1221670 | doi = 10.1042/bj3540413 }}{{cite journal | vauthors = Gaburjakova M, Gaburjakova J, Reiken S, Huang F, Marx SO, Rosemblit N, Marks AR | title = FKBP12 binding modulates ryanodine receptor channel gating | journal = The Journal of Biological Chemistry | volume = 276 | issue = 20 | pages = 16931–5 | date = May 2001 | pmid = 11279144 | doi = 10.1074/jbc.M100856200 | doi-access = free }}
• HOMER1{{cite journal | vauthors = Hwang SY, Wei J, Westhoff JH, Duncan RS, Ozawa F, Volpe P, Inokuchi K, Koulen P | title = Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling | journal = Cell Calcium | volume = 34 | issue = 2 | pages = 177–84 | date = August 2003 | pmid = 12810060 | doi = 10.1016/S0143-4160(03)00082-4 }}
• HOMER2{{cite journal | vauthors = Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF, Pessah IN | title = Homer regulates gain of ryanodine receptor type 1 channel complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 44722–30 | date = November 2002 | pmid = 12223488 | doi = 10.1074/jbc.M207675200 | doi-access = free }}
• HOMER3 and
• TRDN.{{cite journal | vauthors = Lee JM, Rho SH, Shin DW, Cho C, Park WJ, Eom SH, Ma J, Kim DH | title = Negatively charged amino acids within the intraluminal loop of ryanodine receptor are involved in the interaction with triadin | journal = The Journal of Biological Chemistry | volume = 279 | issue = 8 | pages = 6994–7000 | date = February 2004 | pmid = 14638677 | doi = 10.1074/jbc.M312446200 | doi-access = free }}{{cite journal | vauthors = Caswell AH, Motoike HK, Fan H, Brandt NR | title = Location of ryanodine receptor binding site on skeletal muscle triadin | journal = Biochemistry | volume = 38 | issue = 1 | pages = 90–7 | date = January 1999 | pmid = 9890886 | doi = 10.1021/bi981306+ }}{{cite journal | vauthors = Guo W, Campbell KP | title = Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum | journal = The Journal of Biological Chemistry | volume = 270 | issue = 16 | pages = 9027–30 | date = April 1995 | pmid = 7721813 | doi = 10.1074/jbc.270.16.9027 | doi-access = free }}{{cite journal | vauthors = Groh S, Marty I, Ottolia M, Prestipino G, Chapel A, Villaz M, Ronjat M | title = Functional interaction of the cytoplasmic domain of triadin with the skeletal ryanodine receptor | journal = The Journal of Biological Chemistry | volume = 274 | issue = 18 | pages = 12278–83 | date = April 1999 | pmid = 10212196 | doi = 10.1074/jbc.274.18.12278 | doi-access = free }}

• Ryanodine receptor

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• {{cite journal | vauthors = Treves S, Anderson AA, Ducreux S, Divet A, Bleunven C, Grasso C, Paesante S, Zorzato F | title = Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders | journal = Neuromuscular Disorders | volume = 15 | issue = 9–10 | pages = 577–87 | date = October 2005 | pmid = 16084090 | doi = 10.1016/j.nmd.2005.06.008 | s2cid = 31372661 }}

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• {{MeshName|RYR1+protein,+human}}
• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mmd GeneReviews/NIH/UW entry on Multiminicore Disease]
• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mhs GeneReviews/NCBI/NIH/UW entry on Malignant Hyperthermia Susceptibility]
• [http://www.dmd.nl/nmdb2/home.php?select_db=RYR1 RYR1 Variation Database ] {{Webarchive|url=https://web.archive.org/web/20120301201847/http://www.dmd.nl/nmdb2/home.php?select_db=RYR1 |date=2012-03-01 }}

{{PDB Gallery|geneid=6261}}

{{Ion channels|g1}}

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Category:Ion channels

Category:Muscle stabilizers