Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

Leong, P. C.; MacLennan, David H.

doi:10.1139/bcb-76-5-681

Cited by 27 publications

(23 citation statements)

References 107 publications

(178 reference statements)

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“…A region nearby in the sequence involving residues 1076 -1122 appears also to be important and to play a role in the interaction of RyR1 with the voltage sensors/dihydropyridine receptors (32,33,44). Based largely upon freezefracture studies of skeletal muscle sarcolemma/transverse tubules and SR, Franzini-Armstrong and co-workers (46) have proposed a structural model for the triad junction, regions where the transverse tubules and SR form junctions to carry out excitation-contraction coupling.…”

Section: Fig 6 Comparison Of Ryr3 and Ryr1 Reconstructionsmentioning

confidence: 99%

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Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy

Sharma¹,

Jeyakumar²,

Fleischer³

et al. 2000

Journal of Biological Chemistry

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Using cryo-electron microscopy and single particle image processing techniques, we present the first threedimensional reconstructions of isoform 3 of the ryanodine receptor/calcium release channel (RyR3). Reconstructions were carried out on images obtained from a purified, detergent-solubilized receptor for two different buffer conditions, which were expected to favor open and closed functional states of the channel. As for the heart (RyR2) and skeletal muscle (RyR1) receptor isoforms, RyR3 is a homotetrameric complex comprising two main components, a multidomain cytoplasmic assembly and a smaller (ϳ20% of the total mass) transmembrane region. Although the isoforms show structural similarities, consistent with the ϳ70% overall sequence identity of the isoforms, detailed comparisons of RyR3 with RyR1 showed one region of highly significant difference between them. This difference indicated additional mass present in RyR1, and it likely corresponds to a region of the RyR1 sequence (residues 1303-1406, known as diversity region 2) that is absent from RyR3. The reconstructions of RyR3 determined under "open" and "closed" conditions were similar to each other in overall architecture. A difference map computed between the two reconstructions reveals subtle changes in conformation at several widely dispersed locations in the receptor, the most prominent of which is a ϳ4°ro-tation of the transmembrane region with respect to the cytoplasmic assembly.

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Section: Fig 6 Comparison Of Ryr3 and Ryr1 Reconstructionsmentioning

confidence: 99%

“…To whom correspondence should be addressed. idues 1872-1923), seem to be involved in establishing the properties of excitation-contraction coupling that are characteristic of skeletal muscle vis-à -vis cardiac muscle (30,31), although other regions are also important (32,33).…”

mentioning

confidence: 99%

Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy

Sharma¹,

Jeyakumar²,

Fleischer³

et al. 2000

Journal of Biological Chemistry

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“…Two well-character-ized Ca 2ϩ -channel complexes represent the central elements of this excitation-contraction coupling process: the voltage-sensing dihydropyridine receptor (8) and the ryanodine receptor (RyR) Ca 2ϩ release channel (20). In skeletal muscle, both receptors directly interact during signal transduction at the triad junction (42), whereas, in developing skeletal muscle and cardiac fibers, a Ca 2ϩ -induced Ca 2ϩ release mechanism appears to be the dominant process (7). The skeletal muscle dihydropyridine receptor consists of the principal ␣ 1S -subunit, which contains the voltage-sensing domain and the pore-forming structures, as well as the auxiliary subunits ␣ 2 ␦, -␤, and -␥, which have important regulatory functions (30).…”

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confidence: 99%

Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophicmdxmuscle

Culligan

Banville

Dowling

et al. 2002

Journal of Applied Physiology

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Although the reduction in dystrophin-associated glycoproteins is the primary pathophysiological consequence of the deficiency in dystrophin, little is known about the secondary abnormalities leading to x-linked muscular dystrophy. As abnormal Ca2+ handling may be involved in myonecrosis, we investigated the fate of key Ca2+ regulatory membrane proteins in dystrophic mdx skeletal muscle membranes. Whereas the expression of the ryanodine receptor, the dihydropyridine receptor, the Ca2+-ATPase, and calsequestrin was not affected, a drastic decline in calsequestrin-like proteins of 150–220 kDa was observed in dystrophic microsomes using one-dimensional immunoblotting, two-dimensional immunoblotting with isoelectric focusing, diagonal two-dimensional blotting technique, and immunoprecipitation. In analogy, overall Ca2+ binding was reduced in the sarcoplasmic reticulum of dystrophic muscle. The reduction in Ca2+ binding proteins might be directly involved in triggering impaired Ca2+ sequestration within the lumen of the sarcoplasmic reticulum. Thus disturbed sarcolemmal Ca2+ fluxes seem to influence overall Ca2+homeostasis, resulting in distinct changes in the expression profile of a subset of Ca2+ handling proteins, which might be an important factor in the progressive functional decline of dystrophic muscle fibers.

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“…9 Following voltage sensing by the ␣ 1 -subunit of the dihydropyridine receptor, 10 direct physical triad receptor coupling triggers Ca 2ϩ efflux through the ryanodine receptor. 11 The energy-dependent reuptake of Ca 2ϩ ions is achieved by Ca 2ϩ pumps of the longitudinal tubules and the terminal cisternae. 12 Within the lumen of the sarcoplasmic reticulum, the high-capacity Ca 2ϩ -binding protein calsequestrin (CSQ) 13 acts as an ion reservoir and endogenous regulator of Ca 2ϩ efflux.…”

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Ca 2+ -regulatory muscle proteins in the alcohol-fed rat

et al. 2003

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Alcoholic myopathy is characterized by muscle weakness and difficulties in gait and locomotion. It is one of the most prevalent skeletal muscle disorders in the Western hemisphere, affecting between 40% and 60% of all chronic alcohol misusers. However, the pathogenic mechanisms are unknown, although recent studies have suggested that membrane defects occur as a consequence of chronic alcohol exposure. It was our hypothesis that alcohol ingestion perturbs membranelocated proteins associated with intracellular signalling and contractility, in particular those relating to calcium homeostasis. To test this, we fed male Wistar rats nutritionally complete liquid diets containing ethanol as 35% of total dietary energy. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 6 weeks, rats were killed and skeletal muscles dissected. These were used to determine important ion-regulatory skeletal muscle proteins including sarcalumenin (SAR), sarcoplasmic-endoplasmic reticulum Ca 2؉ -adenosine triphosphatase (ATPase) (SERCA1), the junctional face protein of 90 kd (90-JFP), ␣ 1 -and ␣ 2 -dihydropyridine receptor (␣ 1 -DHPR and ␣ 2 -DHPR), and calsequestrin (CSQ) by immunoblotting. The relative abundance of microsomal proteins was determined by immunoblotting using the enhanced chemiluminescence (ECL) technique. The data showed that alcohol-feeding significantly reduced gastrocnemius and hind limb muscle weights (P < .05 in both instances). Concomitant changes included increases in the relative amounts of SERCA1 (P < .05) and Ca 2؉ -ATPase activity (P < .025). However, there were no statistically significant changes in either SAR, 90-JFP, ␣ 1 -DHPR or ␣ 2 -DHPR (P > .2 in all instances). Reductions in CSQ were of marginal significance (P ‫؍‬ .0950). We conclude that upregulation of SERCA1 protein and Ca 2؉ -ATPase activity may be an adaptive mechanism and/or a contributory process in the pathology of alcohol-induced muscle disease.

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Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

Cited by 27 publications

References 107 publications

Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy

Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy

Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophicmdxmuscle

Ca 2+ -regulatory muscle proteins in the alcohol-fed rat

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