Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.10.244152v1?rss=1 Authors: Jones, F. K., Phillips, A., Jones, A. R., Pisconti, A. Abstract: Muscle stem cells (MuSCs) are indispensable for muscle regeneration. A multitude of extracellular stimuli affect MuSCs from quiescent progenitors to differentiated myocytes, the activity of which is modulated by coreceptors such as syndecan-3 (SDC3). Here we investigated the global landscape of SDC3-mediated regulation of myogenesis using a phosphoproteomics approach which revealed, with the precision level of individual phosphosites, the large-scale extent of SDC3-mediated regulation of MuSC signal transduction. We then focused on INSR/AKT/mTOR as a key pathway regulated by SDC3 during myogenesis and mechanistically dissected SDC3-mediated inhibition of insulin signalling in MuSCs. SDC3 interacts with INSR limiting insulin signal transduction via INSR/AKT/mTOR. Both knockdown of INSR and inhibition of AKT rescue Sdc3-/- MuSC differentiation to wild type levels. Since SDC3 is rapidly downregulated at the onset of differentiation, our study suggests that SDC3 acts a timekeeper to maintain proliferating MuSC response to insulin to low levels and prevent premature differentiation. Copy rights belong to original authors. Visit the link for more info