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. Regulatory associated protein of mTOR (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. In the present paper, we show that in muscle-specific raptor knockout (RamKO), the bulk of glycogen phosphorylase (GP) is mainly associated in its cAMP-non-stimulated form with sarcoplasmic reticulum (SR) membranes. In addition, 3[H]–ryanodine and 3[H]–PN200-110 equilibrium binding show a ryanodine to dihydropyridine receptors (DHPRs) ratio of 0.79 and 1.35 for wild-type (WT) and raptor KO skeletal muscle membranes respectively. Peak amplitude and time to peak of the global calcium transients evoked by supramaximal field stimulation were not different between WT and raptor KO. However, the increase in 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 flexor digitorum brevis (FDB) fibres from raptor KO. The present study shows that the protein composition and function of the molecular machinery involved in skeletal muscle excitation–contraction (E–C) coupling is affected by mTORC1 signalling.
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Research Article|
February 06 2015
Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation–contraction coupling supramolecular complex
Rubén J. Lopez;
Rubén J. Lopez
*Departments of Anesthesia and of Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
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Barbara Mosca;
Barbara Mosca
*Departments of Anesthesia and of Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
†Department of Life Sciences, General Pathology section, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy
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Susan Treves;
Susan Treves
*Departments of Anesthesia and of Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
†Department of Life Sciences, General Pathology section, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy
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Marcin Maj;
Marcin Maj
*Departments of Anesthesia and of Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
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Leda Bergamelli;
Leda Bergamelli
†Department of Life Sciences, General Pathology section, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy
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Juan C. Calderon;
Juan C. Calderon
‡Laboratorio de Fisiología Celular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, 1020A Caracas, Venezuela
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C. Florian Bentzinger;
C. Florian Bentzinger
§Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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Klaas Romanino;
Klaas Romanino
§Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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Michael N. Hall;
Michael N. Hall
§Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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Markus A. Rüegg;
Markus A. Rüegg
§Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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Osvaldo Delbono;
Osvaldo Delbono
║Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, U.S.A.
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Carlo Caputo;
Carlo Caputo
‡Laboratorio de Fisiología Celular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, 1020A Caracas, Venezuela
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Francesco Zorzato
Francesco Zorzato
1
*Departments of Anesthesia and of Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
†Department of Life Sciences, General Pathology section, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy
1To whom correspondence should be addressed (email zor@unife.it).
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Publisher: Portland Press Ltd
Received:
July 23 2014
Revision Received:
November 26 2014
Accepted:
November 28 2014
Accepted Manuscript online:
November 28 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem J (2015) 466 (1): 123–135.
Article history
Received:
July 23 2014
Revision Received:
November 26 2014
Accepted:
November 28 2014
Accepted Manuscript online:
November 28 2014
Citation
Rubén J. Lopez, Barbara Mosca, Susan Treves, Marcin Maj, Leda Bergamelli, Juan C. Calderon, C. Florian Bentzinger, Klaas Romanino, Michael N. Hall, Markus A. Rüegg, Osvaldo Delbono, Carlo Caputo, Francesco Zorzato; Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation–contraction coupling supramolecular complex. Biochem J 15 February 2015; 466 (1): 123–135. doi: https://doi.org/10.1042/BJ20140935
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