Proteomics

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Nerve activity inhibits mTORC1-dependent protein synthesis in skeletal muscle


ABSTRACT: To find out intracellular signaling pathways regulting fiber type specific muscle wasting we generated a new mouse model, which allows us to label specifically muscle proteins. Interestingly, we observed that loss of muscle activity by denervation induces a strong increase of protein labeling in oxidative, mitochondria-rich muscle fibers. MS-based analysis, rapamycin treatments and genetic models showed requirement of mTORC1 signaling for increased protein synthesis in dependence of nerve activity.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Leg Muscle

SUBMITTER: Frederik Tellkamp  

LAB HEAD: Bert Blaauw

PROVIDER: PXD056544 | Pride | 2025-05-07

REPOSITORIES: Pride

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Publications

Neural stimulation suppresses mTORC1-mediated protein synthesis in skeletal muscle.

Dumitras Ana G AG   Piccoli Giorgia G   Tellkamp Frederik F   Keufgens Lena L   Baraldo Martina M   Zorzato Sabrina S   Cussonneau Laura L   Nogara Leonardo L   Krüger Marcus M   Blaauw Bert B  

Science advances 20250402 14


Skeletal muscle fibers are classified as glycolytic or oxidative, with differing susceptibilities to muscle wasting. However, the intracellular signaling pathways regulating fiber-specific muscle trophism remain unclear because of a lack of experimental models measuring protein synthesis. We developed a mouse model overexpressing a mutated transfer RNA synthetase in muscle fibers, enabling specific protein labeling using an artificial methionine substitute, which can be revealed through click ch  ...[more]

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