Dual Regulation of the Skeletal Muscle Ryanodine Receptor by Triadin and Calsequestrin

Ohkura, Masamichi; Furukawa, Ken‐Ichi; Fujimori, Hiroaki; Kuruma, Akinori; Kawano, Seiko; Hiraoka, Masayasu; Kuniyasu, Akihiko; Nakayama, Hitoshi; Ohizumi, Yasushi

doi:10.1021/bi972803d

Cited by 96 publications

(87 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since its initial discovery in 1990 , triadin has been shown to be enriched and embedded in the SR membrane of the triad (Knudson et al, 1993a), to interact directly with both CSQ and RyR1 (Guo and Campbell, 1995), to inhibit RyR channels when applied to the cytoplasmic side (Ohkura et al, 1998), to activate channels when applied to the luminal side (Gyorke et al, 2004), and to contribute to the luminal Ca 2+ transduction machinery that regulates Ca 2+ release channel activity in skeletal muscle (Beard et al, 2004). Lee et al (2004) identifi ed three negatively charged amino acids (D4878, D4907, and E4908) in an RyR1 luminal loop that were each required for the isolated loop to bind a specifi c positively charged triadin KEKE motif (residues Fig.…”

Section: Discussionmentioning

confidence: 99%

“…These results demonstrate a strong functional consequence of triadin binding to WT RyR1 and the lack of any functional change when triadin is added to triadin binding-defi cient ∆M 1,2,3 channels. Previous studies have shown an inhibitory interaction between the cytoplasmic domain of triadin and RyR1 (Ohkura et al, 1998;Groh et al, 1999).…”

Section: Ryr1 Mutations That Disrupt Triadin Binding Do Not Directly mentioning

confidence: 90%

See 1 more Smart Citation

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

Beard¹,

Groom²,

Kimura³

et al. 2007

J Cell Biol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Ryr1 Mutations That Disrupt Triadin Binding Do Not Directly mentioning

confidence: 90%

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

Beard¹,

Groom²,

Kimura³

et al. 2007

J Cell Biol

View full text Add to dashboard Cite

“…In skeletal muscle, triadin has been shown to inhibit the calcium channel activity of purified RyR (18,19). These experiments were the first to identify a function of triadin in skeletal muscle, and they led to the conclusion that triadin could regulate RyR function via inhibition of the channel.…”

mentioning

confidence: 98%

Triadin (Trisk 95) Overexpression Blocks Excitation-Contraction Coupling in Rat Skeletal Myotubes

Rezgui

Vassilopoulos

Brocard

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

To identify the function of triadin in skeletal muscle, adenovirusmediated overexpression of Trisk 95 or Trisk 51, the two major skeletal muscle isoforms, was induced in rat skeletal muscle primary cultures, and the physiological behavior of the modified cells was analyzed. Overexpression did not modify the expression level of their protein partners ryanodine receptor, dihydropyridine receptor, and the other triadin. Caffeine-induced calcium release was also unaffected by triadin overexpression. Nevertheless, in the absence of extracellular calcium, depolarization-induced calcium release was almost abolished in Trisk 95 overexpressing myotubes (T95 myotubes), and not modified in Trisk 51 overexpressing myotubes (T51 myotubes). This was not because of a modification of dihydropyridine receptors, as depolarization in presence of external calcium still induced a calcium release, and the activation curve of dihydropyridine receptor was unchanged, in both T95 and T51 myotubes. The calcium release complex was also maintained in T95 myotubes as Trisk 95, ryanodine receptor, dihydropyridine receptor, and Trisk 51 were still co-localized. The effect of Trisk 95 overexpression on depolarization-induced calcium release was reversed by a simultaneous infection with an antisense Trisk 95 adenovirus, indicating the specificity of this effect. Thus, the level of Trisk 95 and not Trisk 51 is important on regulating the calcium release complex, and an excess of this protein can lead to an inhibition of the physiological function of the complex. In skeletal muscle cells, excitation-contraction (E-C)2 coupling is the process by which depolarization of the plasma membrane produces a large transient release of Ca 2ϩ from the sarcoplasmic reticulum, which in turn triggers contraction. Dihydropyridine receptors (DHPRs), the L-type Ca 2ϩ channels localized in the T-tubule membrane, serve as the voltage sensors for E-C coupling (1, 2) and activate ryanodine receptors (RyRs), the intracellular Ca 2ϩ release channels of the sarcoplasmic reticulum membrane (3, 4). In skeletal muscle, entry of Ca 2ϩ through DHPR is not required for E-C coupling (5). Instead, a voltage-dependent conformational change in the II-III loop of the skeletal muscle DHPR ␣1 subunit (Cav1.1) activates the skeletal muscle ryanodine receptor, RyR1. Activation of RyR1 results in a release of Ca 2ϩ from the sarcoplasmic reticulum intracellular stores into the cytosol, which in turn activates the cellular contractile apparatus to initiate muscle contraction. In cardiac muscle, the entry of external calcium through DHPR is required to induce activation of RyR and release of internal Ca 2ϩ via RyR, a mechanism known as calcium-induced calcium release. Calcium-induced calcium release is not the initial mechanism responsible of Ca 2ϩ release in skeletal muscle, but it can contribute to the amplification of the signal, and both calcium-induced calcium release and conformational coupling are involved in skeletal muscle contraction, to different extents (6).Triadin is a transmem...

show abstract

“…Beyond simply anchoring calsequestrin to the ryanodine receptor, triadin may affect the channel activity of the ryanodine receptor directly. For example, application of skeletal muscle triadin to the purified ryanodine receptor incorporated in planar lipid bilayers inhibits the channel activity of the protein (18,19). As part of a program to better understand the function of junctional SR proteins in myocardium, we initiated a strategy in which key junctional SR proteins are overexpressed in transgenic mouse hearts.…”

mentioning

confidence: 99%

Cardiac Hypertrophy and Impaired Relaxation in Transgenic Mice Overexpressing Triadin 1

Kirchhefer¹,

Neumann²,

Baba³

et al. 2001

Journal of Biological Chemistry

101

View full text Add to dashboard Cite

Triadin 1 is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum (SR), which forms a quaternary complex with the ryanodine receptor (Ca 2؉ release channel), junctin, and calsequestrin. To better understand the role of triadin 1 in excitation-contraction coupling in the heart, we generated transgenic mice with targeted overexpression of triadin 1 to mouse atrium and ventricle, employing the ␣-myosin heavy chain promoter to drive protein expression. The protein was overexpressed 5-fold in mouse ventricles, and overexpression was accompanied by cardiac hypertrophy. The levels of two other junctional SR proteins, the ryanodine receptor and junctin, were reduced by 55% and 73%, respectively, in association with triadin 1 overexpression, whereas the levels of calsequestrin, the Ca 2؉ -binding protein of junctional SR, and of phospholamban and SERCA2a, Ca 2؉ -handling proteins of the free SR, were unchanged. Cardiac myocytes from triadin 1-overexpressing mice exhibited depressed contractility; Ca 2؉ transients decayed at a slower rate, and cell shortening and relengthening were diminished. The extent of depression of cell shortening of triadin 1-overexpressing cardiomyocytes was rate-dependent, being more depressed under low stimulation frequencies (0.5 Hz), but reaching comparable levels at higher frequencies of stimulation (5 Hz). Spontaneously beating, isolated work-performing heart preparations overexpressing triadin 1 also relaxed at a slower rate than control hearts, and failed to adapt to increased afterload appropriately. The fast time inactivation constant, 1 , of the L-type Ca 2؉ channel was prolonged in transgenic cardiomyocytes. Our results provide evidence for the coordinated regulation of junctional SR protein expression in heart independent of free SR protein expression, and furthermore suggest an important role for triadin 1 in regulating the contractile properties of the heart during excitation-contraction coupling.

show abstract

Dual Regulation of the Skeletal Muscle Ryanodine Receptor by Triadin and Calsequestrin

Cited by 96 publications

References 35 publications

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

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

Triadin (Trisk 95) Overexpression Blocks Excitation-Contraction Coupling in Rat Skeletal Myotubes

Cardiac Hypertrophy and Impaired Relaxation in Transgenic Mice Overexpressing Triadin 1

Contact Info

Product

Resources

About