Sarcolipin orchestrates calcium signaling to regulate muscle metabolism (1162.1)

Abstract

Sarcolipin(SLN) is 31 amino acid long protein that regulates the Sarcoplasmic reticulum calcium ATPase (SERCA) activity in skeletal and cardiac muscle. Recently, our lab identified that SLN plays an important role in muscle‐based thermogenesis. Mice lacking SLN are cold sensitive and susceptible to diet induced obesity. Interestingly SLN is induced in skeletal muscle during neonatal development, high fat diet, muscle dystrophies, and inflammation. Since these are the states of increased oxidative metabolism in skeletal muscle we hypothesize that SLN is recruited to maintain this oxidative phenotype. Here we show that SLN overexpressing muscle fibers have high resting calcium and increased recruitment of calcium mediated signaling when there is increased demand. To determine the mechanism regulating SLN induction and downstream signaling we made use of C2C12 cells. We show that inhibiting the calcium signaling pathways regulated by calcineurin downregulates the expression of SLN. Based on our data we propose that SLN forms a feedback loop with calcium mediated signaling pathways and plays an important role to support the oxidative metabolism in skeletal muscle.Grant Funding Source: Supported by NIH, MDA