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Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation-contraction coupling supramolecular complex

Lopez, Rubén J. and Mosca, Barbara and Treves, Susan and Maj, Marcin and Bergamelli, Leda and Calderon, Juan C. and Bentzinger, C. Florian and Romanino, Klaas and Hall, Michael N. and Rüegg, Markus A. and Delbono, Osvaldo and Caputo, Carlo and Zorzato, Francesco. (2015) Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation-contraction coupling supramolecular complex. Biochemical Journal, 466 (1). pp. 123-135.

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Official URL: http://edoc.unibas.ch/dok/A6328832

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Abstract

The protein mammalian target of rapamycin (mTOR) is a serine/threonine kinase regulating a number of biochemical pathways controlling cell growth. mTOR exists in two complexes termed mTORC1 and mTORC2. Raptor is associated with mTORC1 and is essential for its function. Ablation of Raptor in skeletal muscle results in several phenotypic changes including decreased life expectancy, increased glycogen deposits and alterations of the twitch kinetics of slow fibres. Here we show that in muscle specific raptor knock-out the bulk of glycogen phosphorylase is mainly associated in its cAMP-non stimulated form with sarcoplasmic reticulum membranes. In addition, 3[H]-ryanodine and 3[H]-PN200-110 equilibrium binding show a ryanodine to dihydropyridine receptors ratio of 0.79 and 1.35 for wild type and raptor knock-out skeletal muscle membranes, respectively. Peak amplitude and time to peak of the global calcium transients evoked by supramaximal field stimulation were not different between wild type and raptor knock-out. However, the increase of the voltage sensor-uncoupled RyRs leads to an increase of both frequency and mass of elementary calcium release events (ECRE) induced by hyper-osmotic shock in FDB fibres from raptor knock-out. This study shows that the protein composition and function of the molecular machinery involved in skeletal muscle excitation-contraction coupling is affected by mTORC1 signaling.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Treves, Susan and Zorzato, Francesco and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Portland Press
ISSN:0264-6021
e-ISSN:1470-8728
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:06 Nov 2018 18:41
Deposited On:10 Apr 2015 09:13

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