This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perez, C. F. Articles by Allen, P. D. Search for Related Content PubMed PubMed Citation Articles by Perez, C. F. Articles by Allen, P. D.

RyR1/RyR3 Chimeras Reveal that Multiple Domains of RyR1 Are Involved in Skeletal-Type E-C Coupling

Claudio F. Perez^*, Andrew Voss, Isaac N. Pessah and Paul D. Allen^*

^* Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and Department of Molecular Biosciences, University of California, Davis, California

Correspondence: Address reprint requests to Claudio F. Perez, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Tel.: 617-732-6881; Fax: 617-732-6927; E-mail: cperez{at}zeus.bwh.harvard.edu.

Skeletal-type E-C coupling is thought to require a direct interaction between RyR1 and the _1S-DHPR. Most available evidence suggests that the cytoplasmic II–III loop of the dihydropyridine receptor (DHPR) is the primary source of the orthograde signal. However, identification of the region(s) of RyR1 involved in bidirectional signaling with the _1S-DHPR remains elusive. To identify these regions we have designed a series of chimeric RyR cDNAs in which different segments of RyR1 were inserted into the corresponding region of RyR3 and expressed in dyspedic 1B5 myotubes. RyR3 provides a preferable background than RyR2 for defining domains essential for E-C coupling because it possesses less sequence homology to RyR1 than the RyR2 backbone used in previous studies. Our data show that two regions of RyR1 (chimera Ch-10 aa 1681–2641 and Ch-9 aa 2642–3770), were independently able to restore skeletal-type E-C coupling to RyR3. These two regions were further mapped and the critical RyR1 residues were 1924–2446 (Ch-21) and 2644–3223 (Ch-19). These results both support and refine the previous hypothesis that multiple domains of RyR1 combine to functionally interact with the DHPR during E-C coupling.

This article has been cited by other articles:

				A. R. Jacobson, S. T. Moe, P. D. Allen, and J. D. Fessenden Structural Determinants of 4-Chloro-m-cresol Required for Activation of Ryanodine Receptor Type 1 Mol. Pharmacol., July 1, 2006; 70(1): 259 - 266. [Abstract] [Full Text] [PDF]

				Z. Liu, R. Wang, J. Zhang, S. R. W. Chen, and T. Wagenknecht Localization of a Disease-associated Mutation Site in the Three-dimensional Structure of the Cardiac Muscle Ryanodine Receptor J. Biol. Chem., November 11, 2005; 280(45): 37941 - 37947. [Abstract] [Full Text] [PDF]

				A. M. Hurne, J. J. O'Brien, D. Wingrove, G. Cherednichenko, P. D. Allen, K. G. Beam, and I. N. Pessah Ryanodine Receptor Type 1 (RyR1) Mutations C4958S and C4961S Reveal Excitation-coupled Calcium Entry (ECCE) Is Independent of Sarcoplasmic Reticulum Store Depletion J. Biol. Chem., November 4, 2005; 280(44): 36994 - 37004. [Abstract] [Full Text] [PDF]

				C. F. Perez, J. R. Lopez, and P. D. Allen Expression levels of RyR1 and RyR3 control resting free Ca2+ in skeletal muscle Am J Physiol Cell Physiol, March 1, 2005; 288(3): C640 - C649. [Abstract] [Full Text] [PDF]

				C. Paolini, J. D. Fessenden, I. N. Pessah, and C. Franzini-Armstrong Evidence for conformational coupling between two calcium channels PNAS, August 24, 2004; 101(34): 12748 - 12752. [Abstract] [Full Text] [PDF]

				G. Kugler, R. G. Weiss, B. E. Flucher, and M. Grabner Structural Requirements of the Dihydropyridine Receptor {alpha}1S II-III Loop for Skeletal-type Excitation-Contraction Coupling J. Biol. Chem., February 6, 2004; 279(6): 4721 - 4728. [Abstract] [Full Text] [PDF]

				A. Shtifman, C. Paolini, J. R. Lopez, P. D. Allen, and F. Protasi Ca2+ influx through {alpha}1S DHPR may play a role in regulating Ca2+ release from RyR1 in skeletal muscle Am J Physiol Cell Physiol, January 1, 2004; 286(1): C73 - C78. [Abstract] [Full Text] [PDF]

				E. H. Lee, J. R. Lopez, J. Li, F. Protasi, I. N. Pessah, D. H. Kim, and P. D. Allen Conformational coupling of DHPR and RyR1 in skeletal myotubes is influenced by long-range allosterism: evidence for a negative regulatory module Am J Physiol Cell Physiol, January 1, 2004; 286(1): C179 - C189. [Abstract] [Full Text] [PDF]

				D. C. Sheridan, L. Carbonneau, C. A. Ahern, P. Nataraj, and R. Coronado Ca2+-Dependent Excitation-Contraction Coupling Triggered by the Heterologous Cardiac/Brain DHPR {beta}2a-Subunit in Skeletal Myotubes Biophys. J., December 1, 2003; 85(6): 3739 - 3757. [Abstract] [Full Text] [PDF]

				C. F. Perez, S. Mukherjee, and P. D. Allen Amino Acids 1-1,680 of Ryanodine Receptor Type 1 Hold Critical Determinants of Skeletal Type for Excitation-Contraction Coupling: ROLE OF DIVERGENCE DOMAIN D2 J. Biol. Chem., October 10, 2003; 278(41): 39644 - 39652. [Abstract] [Full Text] [PDF]

				J. D. Fessenden, C. F. Perez, S. Goth, I. N. Pessah, and P. D. Allen Identification of a Key Determinant of Ryanodine Receptor Type 1 Required for Activation by 4-Chloro-m-cresol J. Biol. Chem., August 1, 2003; 278(31): 28727 - 28735. [Abstract] [Full Text] [PDF]