Protein arginine methyltransferase expression, localization, and activity during disuse-induced skeletal muscle plasticity. Academic Article uri icon

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abstract

  • Protein arginine methyltransferase 1 (PRMT1), PRMT4, and PRMT5 catalyze the methylation of arginine residues on target proteins. Previous work suggests that these enzymes regulate skeletal muscle plasticity. However, the function of PRMTs during disuse-induced muscle remodeling is unknown. The purpose of our study was to determine whether denervation-induced muscle disuse alters PRMT expression and activity in skeletal muscle, as well as to contextualize PRMT biology within the early disuse-evoked events that precede atrophy, which remain largely undefined. Mice were subjected to 6, 12, 24, 72, or 168 h of unilateral hindlimb denervation. Muscle mass decreased by ~30% after 72 or 168 h of neurogenic disuse, depending on muscle fiber type composition. The expression, localization, and activities of PRMT1, PRMT4, and PRMT5 were modified, exhibiting changes in gene expression and activity that were PRMT-specific. Rapid alterations in canonical muscle atrophy signaling such as forkhead box protein O1, muscle RING-finger protein-1, as well as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) content, AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase, were observed before measurable decrements in muscle mass. Denervation-induced modifications in AMPK-PRMT1 and PGC-1α-PRMT1 binding revealed a novel, putative PRMT1-AMPK-PGC-1α signaling axis in skeletal muscle. Here, PGC-1α-PRMT1 binding was elevated after 6 h of disuse, whereas AMPK-PRMT1 interactions were reduced following 168 h of denervation. Our data suggest that PRMT biology is integral to the mechanisms that precede and initiate skeletal muscle atrophy during conditions of neurogenic disuse. This study furthers our understanding of the role of PRMTs in governing skeletal muscle plasticity.

publication date

  • February 1, 2018