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dc.contributor.authorChen, Yanyien_US
dc.contributor.authorXue, Shenghuien_US
dc.contributor.authorZou, Juanen_US
dc.contributor.authorLopez, Jose R.en_US
dc.contributor.authorYang, Jenny J.en_US
dc.contributor.authorPerez, Claudio F.en_US
dc.date.accessioned2014-07-07T18:14:24Z
dc.date.issued2014en_US
dc.identifier.citationChen, Yanyi, Shenghui Xue, Juan Zou, Jose R. Lopez, Jenny J. Yang, and Claudio F. Perez. 2014. “Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptor.” Biochemical Journal 460 (Pt 2): 261-271. doi:10.1042/BJ20131553. http://dx.doi.org/10.1042/BJ20131553.en
dc.identifier.issn0264-6021en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12406943
dc.description.abstractPassive SR (sarcoplasmic reticulum) Ca2+ leak through the RyR (ryanodine receptor) plays a critical role in the mechanisms that regulate [Ca2+]rest (intracellular resting myoplasmic free Ca2+ concentration) in muscle. This process appears to be isoform-specific as expression of either RyR1 or RyR3 confers on myotubes different [Ca2+]rest. Using chimaeric RyR3–RyR1 receptors expressed in dyspedic myotubes, we show that isoform-dependent regulation of [Ca2+]rest is primarily defined by a small region of the receptor encompassing amino acids 3770–4007 of RyR1 (amino acids 3620–3859 of RyR3) named as the CLR (Ca2+ leak regulatory) region. [Ca2+]rest regulation by the CLR region was associated with alteration of RyRs’ Ca2+-activation profile and changes in SR Ca2+-leak rates. Biochemical analysis using Tb3+-binding assays and intrinsic tryptophan fluorescence spectroscopy of purified CLR domains revealed that this determinant of RyRs holds a novel Ca2+-binding domain with conformational properties that are distinctive to each isoform. Our data suggest that the CLR region provides channels with unique functional properties that modulate the rate of passive SR Ca2+ leak and confer on RyR1 and RyR3 distinctive [Ca2+]rest regulatory properties. The identification of a new Ca2+-binding domain of RyRs with a key modulatory role in [Ca2+]rest regulation provides new insights into Ca2+-mediated regulation of RyRs.en
dc.language.isoen_USen
dc.publisherPortland Press Ltd.en
dc.relation.isversionofdoi:10.1042/BJ20131553en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019983/pdf/en
dash.licenseLAAen_US
dc.subjectcalcium-binding siteen
dc.subjectcalcium leaken
dc.subjectmyotubeen
dc.subjectskeletal muscleen
dc.subjectterbium fluorescenceen
dc.subjecttryptophan fluorescenceen
dc.subject[Caen
dc.subjectCLR, Caen
dc.subjectDHPR, dihydropyridine receptoren
dc.subjectfura 2/AM, fura 2 acetoxymethyl esteren
dc.subjectHEK, human embryonic kidneyen
dc.subjectMHS, malignant hyperthermia syndromeen
dc.subjectRyR, ryanodine receptoren
dc.subjectSERCA1, sarcoplasmic/endoplasmic reticulum Caen
dc.subjectSR, sarcoplasmic reticulumen
dc.titleMyoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptoren
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBiochemical Journalen
dc.date.available2014-07-07T18:14:24Z
dc.identifier.doi10.1042/BJ20131553*


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