The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1

Anderson, Ayuk A.; Altafaj, Xavier; Zheng, Zhenlin; Wang, Zhongmin; Delbono, Osvaldo; Ronjat, Michel; Treves, Susan; Zorzato, Francesco

doi:10.1242/jcs.02935

Cited by 31 publications

(36 citation statements)

References 55 publications

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“…4D) without significantly affecting charge movement half-activation potential (Table 2). These results together with previous studies on JP45 overexpression (30,34) indicate that the stoichiometry of JP45-Ca v 1.1 subunit exhibited by mature skeletal muscle is crucial for maintaining the molecular and functional expression of the Ca v 1.1 subunit (31). Because the Ca v 1.1 charge movement is the activating signal for RyR1-mediated calcium release from the SR, we performed experiments to evaluate whether depolarization-induced calcium release from the SR of JP45 KO mice is also affected.…”

Section: Electrophysiological Properties Of Skeletal Muscle Fibers Frsupporting

confidence: 80%

“…Membrane targeting of Ca v 1.1 depends on amino acid sequences contained within the COOH terminal domain and in the I-II loop of the Ca v 1.1 (20). JP45 interacts with both Ca v 1.1 domains involved in membrane targeting (31), and the lack of these interactions may interfere with either proper Ca v 1.1 membrane targeting or the stabilization of the Ca v 1.1 complex in the T tubular membrane. In conclusion, this study provides new insights into some mechanism(s) responsible for diminished muscle strength.…”

Section: Electrophysiological Properties Of Skeletal Muscle Fibers Frmentioning

confidence: 99%

“…to a pedestal potential of Ϫ50 mV followed by a 25-ms depolarization from Ϫ50 mV to 50 mV with 10-mV intervals (8,31). Intramembrane charge movements were calculated as the integral of the current in response to depolarizing pulses and are expressed per membrane capacitance (coulombs per farad).…”

Section: )] (40)mentioning

confidence: 99%

“…They are involved in (i) calcium storage (calsequestrin) (25), (ii) signal transduction (triadin TD, junctin JC, mitsugumin-29, JP45) (23,24,26,27), (iii) calcium homeostasis (Ca 2ϩ pump, Na/Ca exchanger) (28), and (iv) maintenance of SR spatial organization and integrity (junctophilin) (29). Our previous studies (24,30) demonstrated that JP45, an integral protein constituent of the skeletal muscle SR junctional face membrane, interacts with Ca v 1.1 and the luminal calcium-binding protein calsequestrin (30,31). Ca v 1.1 and JP45 form a complex that is down-regulated during aging and may contribute to decayed muscle strength and physical disability in the elderly (31,32).…”

mentioning

confidence: 99%

“…Our previous studies (24,30) demonstrated that JP45, an integral protein constituent of the skeletal muscle SR junctional face membrane, interacts with Ca v 1.1 and the luminal calcium-binding protein calsequestrin (30,31). Ca v 1.1 and JP45 form a complex that is down-regulated during aging and may contribute to decayed muscle strength and physical disability in the elderly (31,32). On the basis of these initial observations, we reasoned that skeletal muscle strength may depend not only on the composition and functional integrity of the contractile apparatus but also on the molecular composition of the ECC machinery.…”

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confidence: 99%

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Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45

Delbono

Xia²,

Treves³

et al. 2007

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

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Skeletal muscle constitutes Ϸ40% of the human body mass, and alterations in muscle mass and strength may result in physical disability. Therefore, the elucidation of the factors responsible for muscle force development is of paramount importance. Excitationcontraction coupling (ECC) is a process during which the skeletal muscle surface membrane is depolarized, causing a transient release of calcium from the sarcoplasmic reticulum that activates the contractile proteins. The ECC machinery is complex, and the functional role of many of its protein components remains elusive. This study demonstrates that deletion of the gene encoding the sarcoplasmic reticulum protein JP45 results in decreased muscle strength in young mice. Specifically, this loss of muscle strength in JP45 knockout mice is caused by decreased functional expression of the voltage-dependent Ca 2؉ channel Cav1.1, which is the molecule that couples membrane depolarization and calcium release from the sarcoplasmic reticulum. These results point to JP45 as one of the molecules involved in the development or maintenance of skeletal muscle strength.calcium release ͉ excitation-contraction coupling

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Section: Electrophysiological Properties Of Skeletal Muscle Fibers Frsupporting

confidence: 80%

Section: Electrophysiological Properties Of Skeletal Muscle Fibers Frmentioning

confidence: 99%

Section: )] (40)mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45

Delbono

Xia²,

Treves³

et al. 2007

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

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JP-45/JSRP1Variants Affect Skeletal Muscle Excitation-Contraction Coupling by Decreasing the Sensitivity of the Dihydropyridine Receptor

et al. 2012

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JP-45 (also JP45; encoded by JSRP1) is an integral protein constituent of the skeletal muscle sarcoplasmic reticulum junctional face membrane interacting with Cav1.1 (the α.1 subunit of the voltage sensing dihydropyridine receptor, DHPR) and the luminal calcium-binding protein calsequestrin. Two JSRP1 variants have been found in the human population: c.323C>T (p.P108L) in exon 5 and c.449G>C (p.G150A) in exon 6, but nothing is known concerning the incidence of these polymorphisms in the general population or in patients with neuromuscular diseases nor the impact of the polymorphisms on excitation-contraction coupling. In the present report we investigated the frequencies of these two JSRP1 polymorphisms in the Swiss Malignant Hyperthermia population and studied the functional impact of the variants on excitation -contraction coupling. Our results show that the polymorphisms are equally distributed among Malignant Hyperthermia Negative, Malignant Hyperthermia Equivocal and Malignant Hyperthermia Susceptible individuals. Interestingly however, the presence of either one of these JP-45 variants decreased the sensitivity of the dihydropyridine receptor to activation. The presence of a JSRP1 variant may explain the variable phenotype seen in patients with malignant hyperthermia carrying the same mutation and more importantly, may counteract the hypersensitivity of excitation-contraction coupling caused by mutations in the RYR1 gene.

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Excitation-Contraction Coupling Regulation in Aging Skeletal Muscle

Delbono

2010

Sarcopenia – Age-Related Muscle Wasting and Weakness

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The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1

Cited by 31 publications

References 55 publications

Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45

Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45

JP-45/JSRP1Variants Affect Skeletal Muscle Excitation-Contraction Coupling by Decreasing the Sensitivity of the Dihydropyridine Receptor

Excitation-Contraction Coupling Regulation in Aging Skeletal Muscle

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