Jones, Fiona K, Phillips, Alexander M 
ORCID: 0000-0002-1637-4803, Jones, Andrew R and Pisconti, Addolorata
(2022)
The INSR/AKT/mTOR pathway regulates the pace of myogenesis in a syndecan-3-dependent manner.
MATRIX BIOLOGY, 113.
pp. 61-82.
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Abstract
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 restore Sdc3<sup>-/-</sup> 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AKT, Differentiation, Insulin receptor, Insulin signaling, mTOR, Muscle stem cells, Myogenesis, Phosphoproteomics, Proliferation, Proteoglycan, Proteomics, Satellite cells, Syndecan-3, Syndecans |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Dec 2022 12:18 |
| Last Modified: | 21 Sep 2023 01:30 |
| DOI: | 10.1016/j.matbio.2022.09.004 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3166548 |
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