Skeletal muscle mTORC1 regulates neuromuscular junction stability

Area of Science:

• Muscle physiology and molecular signaling
• Neurobiology of muscle function
• Cellular homeostasis and adaptation

Background:

• Skeletal muscle is adaptable, with mTORC1 signaling known to regulate muscle mass and function.
• The precise role of mTORC1 in adult skeletal muscle homeostasis remains unclear.

Purpose of the Study:

• To investigate the role of mTORC1 signaling in adult skeletal muscle homeostasis.
• To determine the effects of disrupting mTORC1 signaling on muscle structure and function.

Main Methods:

• Generated inducible, muscle-specific knockout mice for Raptor and mTOR.
• Analyzed muscle histology and force at 1 and 7 months post-deletion.
• Assessed neuromuscular junction integrity and denervation markers.

Main Results:

• Deletion of Raptor for 7 months caused muscle weakness, regeneration, mitochondrial dysfunction, and autophagy impairment.
• Reduced mTOR signaling induced denervation markers (NCAM), muscle fibrillation, and neuromuscular junction fragmentation.
• Reactivating autophagy prevented mitochondrial dysfunction and denervation in Raptor knockout muscles.

Conclusions:

• mTOR signaling in skeletal muscle fibers is essential for maintaining innervation and neuromuscular junction structure.
• Exercise's benefits for neuromuscular junction pathologies may involve mTORC1 activation in skeletal muscle.