Muscle 4EBP1 activation modifies the structure and function of the neuromuscular junction in mice

• DOI: 10.1038/s41467-022-35547-0
• Publication Date: 2022-12-17T03:05:03Z
• Authors: Seok-Ting J. Ang; Elisa M. Crombie; Han Dong; Kuan-Ting Tan; Adriel Hernando; Dejie Yu; Stuart Adamson; Seonyoung Kim; Dominic J. Withers; Hua Huang; Shih-Yin Tsai
• Keywords: 0301 basic medicine; 570; SYNAPSES; Science; Neuromuscular Junction; 610; Mechanistic Target of Rapamycin Complex 1; Synaptic Transmission; ATROPHY; Article; Mice; 03 medical and health sciences; REVEALS; Animals; Phosphorylation; Adaptor Proteins, Signal Transducing; Science & Technology; Muscles; Q; Multidisciplinary Sciences; CELL-ADHESION MOLECULE; Science & Technology - Other Topics; SKELETAL-MUSCLE; GROWTH; AUTOPHAGY

Abstract Dysregulation of mTOR complex 1 (mTORC1) activity drives neuromuscular junction (NMJ) structural instability during aging; however, downstream targets mediating this effect have not been elucidated. Here, we investigate the roles two mTORC1 phosphorylation for mRNA translation, ribosome protein S6 kinase (S6K1) and eukaryotic translation initiation factor 4E-binding (4EBP1), in regulating NMJ induced by aging sustained activation. While myofiber-specific deletion S6k1 has no on integrity, 4EBP1 activation murine muscle induces drastic morphological remodeling with enhancement synaptic transmission. Mechanistically, modification is attributed to increased satellite cell enhanced post-synaptic acetylcholine receptor (AChR) turnover upon Considering that loss myonuclei reduced are features aging, targeting could induce renewal expanding pool as an alternative intervention mitigate sarcopenia.