Triadin Binding to the C-Terminal Luminal Loop of the Ryanodine Receptor is Important for Skeletal Muscle Excitation–Contraction Coupling

Beard, Nicole A.; Groom, Linda; Kimura, Takashi; Lyfenko, Alla D.; Rosenfeld, Andrew; Marty, Isabelle; Dulhunty, Angela F.; Dirksen, Robert T.

doi:10.1083/jcb1791oia2

Cited by 23 publications

(40 citation statements)

References 34 publications

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“…Available evidence suggests that junctional proteins form a multiprotein complex of high molecular mass, with the RyR1 channel interacting with several junctional proteins, including triadin, JP1, and DHPR (29,30,33). Analysis of the dynamic properties of junctional SR membrane proteins revealed that assembly into clusters is accompanied by a strong reduction of their mobile fraction.…”

Section: Organization and Mobility Properties Of Longitudinal Sr Protmentioning

confidence: 99%

Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells

Cusimano

Pampinella

Giacomello

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The sarcoplasmic reticulum (SR) of skeletal muscle cells is a complex network of tubules and cisternae that share a common lumen delimited by a single continuous membrane. The SR contains longitudinal and junctional domains characterized by distinctive patterns of protein localization, but how SR proteins reach and/or are retained at these sites is not known. Here, we report that the organization of longitudinal SR proteins is a slow process characterized by temporally distinct patterns of protein localization. In contrast, junctional SR proteins rapidly and synchronously assembled into clusters which, however, merged into mature triadic junctions only after completion of longitudinal SR protein organization. Fluorescence recovery after photobleaching experiments indicated that SR organization was accompanied by significant changes in the dynamic properties of longitudinal and junctional proteins. The decrease in mobility that accompanied organization of the longitudinal SR proteins ank1.5-GFP and GFP-InsP3R1 was abrogated by deletion of specific binding sites for myofibrillar or cytoskeletal proteins, respectively. Assembly of junctional SR domains was accompanied by a strong decrease in mobility of junctional proteins that in triadin appeared to be mediated by its intraluminal region. Together, the data suggest that the organization of specific SR domains results from a process of membrane reorganization accompanied by the establishment of multiple protein-protein interactions with intrinsic and extrinsic cues.calcium store ͉ excitation-contraction coupling ͉ muscle differentiation ͉ protein dynamics

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Section: Organization and Mobility Properties Of Longitudinal Sr Protmentioning

confidence: 99%

Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells

Cusimano

Pampinella

Giacomello

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…The lack of an obvious phenotype and the absence of contractile dysfunction in triadin knock‐out mice led to the suggestion that triadins are not essential for E‐C coupling (Shen et al 2007). Nevertheless, RyRs with altered C‐terminal luminal sequences, which interfered with Trisk 95 binding, gave rise to reduced SR calcium release in response to both depolarization and RyR agonists (Goonasekera et al 2007) indicating that triadin binding is crucial for normal RyR function.…”

mentioning

confidence: 99%

Altered expression of triadin 95 causes parallel changes in localized Ca²⁺ release events and global Ca²⁺ signals in skeletal muscle cells in culture

Fodor¹,

Gönczi²,

Sztretye³

et al. 2008

The Journal of Physiology

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The 95 kDa triadin (Trisk 95), an integral protein of the sarcoplasmic reticular membrane in skeletal muscle, interacts with both the ryanodine receptor (RyR) and calsequestrin. While its role in the regulation of calcium homeostasis has been extensively studied, data are not available on whether the overexpression or the interference with the expression of Trisk 95 would affect calcium sparks the localized events of calcium release (LCRE). In the present study LCRE and calcium transients were studied using laser scanning confocal microscopy on C2C12 cells and on primary cultures of skeletal muscle. Liposome-or adenovirus-mediated Trisk 95 overexpression and shRNA interference with triadin translation were used to modify the level of the protein. Stable overexpression in C2C12 cells significantly decreased the amplitude and frequency of calcium sparks, and the frequency of embers. In line with these observations, depolarization-evoked calcium transients were also suppressed. Similarly, adenoviral transfection of Trisk 95 into cultured mouse skeletal muscle cells significantly decreased both the frequency and amplitude of spontaneous global calcium transients. Inhibition of endogenous triadin expression by RNA interference caused opposite effects. Primary cultures of rat skeletal muscle cells expressing endogenous Trisk 95 readily generated spontaneous calcium transients but rarely produced calcium sparks. Their transfection with specific shRNA sequence significantly reduced the triadin-specific immunoreactivity. Functional experiments on these cells revealed that while caffeine-evoked calcium transients were reduced, LCRE appeared with higher frequency. These results suggest that Trisk 95 negatively regulates RyR function by suppressing localized calcium release events and global calcium signals in cultured muscle cells.

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“…Recent research emphasizes the importance of RyR2-triadin interactions for channel function in the heart. In skeletal muscle, triadin knockdown affects voltage-dependent calcium release and reduces muscle function [61,62], whereas disruption of triadin binding reduces both voltage-and ligand-gated SR calcium release, suggesting that triadin may play a role in skeletal muscle EC coupling [63]. The primary triadin binding site on RyR1 as determined by in vitro binding and site-directed mutagenesis is the second intraluminal loop of RyR1 (residues 4861-4918).…”

Section: Reviewmentioning

confidence: 99%

Mapping domains and mutations on the skeletal muscle ryanodine receptor channel

Hwang¹,

Zorzato²,

Clarke³

et al. 2012

Trends in Molecular Medicine

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Triadin Binding to the C-Terminal Luminal Loop of the Ryanodine Receptor is Important for Skeletal Muscle Excitation–Contraction Coupling

Cited by 23 publications

References 34 publications

Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells

Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells

Altered expression of triadin 95 causes parallel changes in localized Ca²⁺ release events and global Ca²⁺ signals in skeletal muscle cells in culture

Mapping domains and mutations on the skeletal muscle ryanodine receptor channel

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Triadin Binding to the C-Terminal Luminal Loop of the Ryanodine Receptor is Important for Skeletal Muscle Excitation–Contraction Coupling

Cited by 23 publications

References 34 publications

Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells

Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells

Altered expression of triadin 95 causes parallel changes in localized Ca2+ release events and global Ca2+ signals in skeletal muscle cells in culture

Mapping domains and mutations on the skeletal muscle ryanodine receptor channel

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Altered expression of triadin 95 causes parallel changes in localized Ca²⁺ release events and global Ca²⁺ signals in skeletal muscle cells in culture