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Publication : Peroxisome proliferator-activated receptor γ coactivator 1α regulates downstream of tyrosine kinase-7 (Dok-7) expression important for neuromuscular junction formation.

First Author  Sugimoto T Year  2024
Journal  Sci Rep Volume  14
Issue  1 Pages  1780
PubMed ID  38245592 Mgi Jnum  J:346032
Mgi Id  MGI:7578489 Doi  10.1038/s41598-024-52198-x
Citation  Sugimoto T, et al. (2024) Peroxisome proliferator-activated receptor gamma coactivator 1alpha regulates downstream of tyrosine kinase-7 (Dok-7) expression important for neuromuscular junction formation. Sci Rep 14(1):1780
abstractText  The neuromuscular junction (NMJ)-formed between a motor nerve terminal and skeletal muscle fiber-plays an important role in muscle contraction and other muscle functions. Aging and neurodegeneration worsen NMJ formation and impair muscle function. Downstream of tyrosine kinase-7 (Dok-7), expressed in skeletal muscle fibers, is essential for the formation of NMJ. Exercise increases the expression of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) in skeletal muscles and restores NMJ formation. In this study, we used skeletal muscle-specific PGC1alpha knockout or overexpression mice to examine the role of PGC1alpha in regulating Dok-7 expression and NMJ formation. Our findings revealed that Dok-7 expression is regulated by PGC1alpha, and luciferase activity of the Dok-7 promoter is greatly increased by coexpressing PGC1alpha and estrogen receptor-related receptor alpha. Thus, we suggest PGC1alpha is involved in exercise-mediated restoration of NMJ formation.
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