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

Abstract

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 γ coactivator 1α (PGC1α) in skeletal muscles and restores NMJ formation. In this study, we used skeletal muscle-specific PGC1α knockout or overexpression mice to examine the role of PGC1α in regulating Dok-7 expression and NMJ formation. Our findings revealed that Dok-7 expression is regulated by PGC1α, and luciferase activity of the Dok-7 promoter is greatly increased by coexpressing PGC1α and estrogen receptor-related receptor α. Thus, we suggest PGC1α is involved in exercise-mediated restoration of NMJ formation.