Author(s): LANFRANCHI, C., ZANOU, N., PLACE, N., Institution: UNIVERSITÉ DE LAUSANNE, Country: SWITZERLAND, Abstract-ID: 1490

INTRODUCTION:
The S100A13 protein is part of the S100A calcium binding protein family, which other members have been associated with a wide variety of cellular processes. We and others have recently highlighted S100A13 as a potential key player in skeletal muscle response to exercise, but its role remains largely unknown.
METHODS:
To investigate the role of S100A13 in skeletal muscle, we used a combination of human, in vitro, and bioinformatics approaches. First, we performed data mining of publicly available proteomic databases to identify exercise modalities influencing S100A13 protein levels. Then, to investigate the specific role of S100A13 in skeletal muscle, we downregulated its level in C2C12 myotubes using siRNA method. On this model, we performed high-resolution respirometry, glucose uptake assay, immunoblotting, and live calcium imaging to characterize the metabolic function and calcium dynamics. Finally, we carried out immunoprecipitation assays on exercising human skeletal muscle tissue to identify S100A13 interactors.
RESULTS:
We observed that S100A13 was among the most upregulated proteins following resistance and intense endurance training. Mitochondrial oxygen consumption and glucose uptake in response to 1 h of electrical pulse stimulation (EPS) were both altered in S100A13-depleted myotubes. We also assessed AMPK phosphorylation levels, which are classically activated in response to exercise and/or metabolic stress. EPS increased AMPK phosphorylation in control cells, but this effect was even stronger in S100A13-depleted cells, suggesting greater metabolic stress. Because S100A13 appeared to impact metabolic processes in our model, we explored potential underlying mechanisms. S100A13 is a calcium -binding protein, and calcium is a key second messenger regulating cellular metabolism. S100A13-depleted myotubes showed a marked deficiency in store-operated calcium entry (SOCE), a process that allows calcium entry from the extracellular space following sarcoplasmic reticulum calcium depletion. Interestingly, in human exercising muscle, the increase in S100A13 protein levels positively correlated with numerous proteins involved in calcium signalling, strongly supporting a potential role for S100A13 in calcium homeostasis during exercise. Consistent with these findings, we identified several S100A13 interactors known to participate in SOCE. Therefore, we hypothesize that S100A13 may form complexes with SOCE-regulating proteins to support muscle function during exercise.
CONCLUSION:
Altogether, our findings suggest that S100A13 coordinates calcium dynamics and the metabolic state of muscle cells. Although speculative, the observed increase in S100A13 protein with exercise training could explain, at least in part, the well-established remodelling of calcium handling and metabolic processes induced by resistance and intense endurance exercise.