| First Author | Jones FK | Year | 2022 |
| Journal | Matrix Biol | Volume | 113 |
| Pages | 61-82 | PubMed ID | 36152781 |
| Mgi Jnum | J:330646 | Mgi Id | MGI:7378095 |
| Doi | 10.1016/j.matbio.2022.09.004 | Citation | Jones FK, et al. (2022) The INSR/AKT/mTOR pathway regulates the pace of myogenesis in a syndecan-3-dependent manner. Matrix Biol |
| abstractText | Muscle stem cells (MuSCs) are indispensable for muscle regeneration. A multitude of extracellular stimuli direct MuSC fate decisions from quiescent progenitors to differentiated myocytes. The activity of these signals is modulated by coreceptors such as syndecan-3 (SDC3). 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 signal transduction in MuSCs. We then focused on INSR/AKT/mTOR as a key pathway regulated by SDC3 during myogenesis and mechanistically dissected SDC3-mediated inhibition of insulin receptor signaling in MuSCs. SDC3 interacts with INSR ultimately limiting signal transduction via 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 restrain proliferating MuSC response and prevent premature differentiation. |
