Universität zu Köln

Baraldo, Martina, Zorzato, Sabrina, Dondjang, Achille Homere Tchampda, Geremia, Alessia, Nogara, Leonardo, Dumitras, Ana Georgia, Canato, Marta, Marcucci, Lorenzo ORCID: 0000-0002-9542-4417, Nolte, Hendrik and Blaauw, Bert . Inducible deletion of raptor and mTOR from adult skeletal muscle impairs muscle contractility and relaxation. J. Physiol.-London. HOBOKEN: WILEY. ISSN 1469-7793

Full text not available from this repository.

Abstract

Skeletal muscle weakness has been associated with different pathological conditions, including sarcopenia and muscular dystrophy, and is accompanied by altered mammalian target f rapamycin (mTOR) signalling. We wanted to elucidate the functional role of mTOR in muscle contractility. Most loss-of-function studies for mTOR signalling have used the drug rapamycin to inhibit some of the signalling downstream of mTOR. However, given that rapamycin does not inhibit all mTOR signalling completely, we generated a double knockout for mTOR and fur the scaffold protein of mTORC1, raptor, in skeletal muscle. We found that double knockout in mice results in a more severe phenotype compared with deletion of raptor or mTOR alone. Indeed, these animals display muscle weakness, increased fibre denervation and a slower muscle relaxation following tetanic stimulation. This is accompanied by a shift towards slow-twitch fibres and changes in the expression levels of calcium-related genes, such as Sercul and Casq1. Double knockout mice show a decrease in calcium decay kinetics after tetanus in vivo, suggestive of a reduced calcium reuptake. In addition, RNA sequencing analysis revealed that many downregulated genes, such as Tcap and Fhod3, arc linked to sarcomere organization. These results suggest a key role Fhod3 mTOR signalling in maintaining proper fibre relaxation in skeletal muscle.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Baraldo, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zorzato, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dondjang, Achille Homere Tchampda UNSPECIFIED UNSPECIFIED UNSPECIFIED Geremia, Alessia UNSPECIFIED UNSPECIFIED UNSPECIFIED Nogara, Leonardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Dumitras, Ana Georgia UNSPECIFIED UNSPECIFIED UNSPECIFIED Canato, Marta UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcucci, Lorenzo UNSPECIFIED orcid.org/0000-0002-9542-4417 UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaauw, Bert UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-675853
DOI:	10.1113/JP283686
Journal or Publication Title:	J. Physiol.-London
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1469-7793
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SARCOPLASMIC-RETICULUM; BINDING PARTNER; RAPAMYCIN; PROTEIN; GROWTH; PHOSPHORYLATION; OVEREXPRESSION; PARVALBUMIN; EXPRESSION; TELETHONIN Multiple languages Neurosciences; Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67585