| First Author | Masson SWC | Year | 2020 |
| Journal | Mol Metab | Volume | 42 |
| Pages | 101091 | PubMed ID | 33011305 |
| Mgi Jnum | J:315965 | Mgi Id | MGI:6714925 |
| Doi | 10.1016/j.molmet.2020.101091 | Citation | Masson SWC, et al. (2020) beta-catenin regulates muscle glucose transport via actin remodelling and M-cadherin binding. Mol Metab 42:101091 |
| abstractText | OBJECTIVE: Skeletal muscle glucose disposal following a meal is mediated through insulin-stimulated movement of the GLUT4-containing vesicles to the cell surface. The highly conserved scaffold-protein beta-catenin is an emerging regulator of vesicle trafficking in other tissues. Here, we investigated the involvement of beta-catenin in skeletal muscle insulin-stimulated glucose transport. METHODS: Glucose homeostasis and transport was investigated in inducible muscle specific beta-catenin knockout (BCAT-mKO) mice. The effect of beta-catenin deletion and mutation of beta-catenin serine 552 on signal transduction, glucose uptake and protein-protein interactions were determined in L6-G4-myc cells, and beta-catenin insulin-responsive binding partners were identified via immunoprecipitation coupled to label-free proteomics. RESULTS: Skeletal muscle specific deletion of beta-catenin impaired whole-body insulin sensitivity and insulin-stimulated glucose uptake into muscle independent of canonical Wnt signalling. In response to insulin, beta-catenin was phosphorylated at serine 552 in an Akt-dependent manner, and in L6-G4-myc cells, mutation of beta-catenin(S552) impaired insulin-induced actin-polymerisation, resulting in attenuated insulin-induced glucose transport and GLUT4 translocation. beta-catenin was found to interact with M-cadherin in an insulin-dependent beta-catenin(S552)-phosphorylation dependent manner, and loss of M-cadherin in L6-G4-myc cells attenuated insulin-induced actin-polymerisation and glucose transport. CONCLUSIONS: Our data suggest that beta-catenin is a novel mediator of glucose transport in skeletal muscle and may contribute to insulin-induced actin-cytoskeleton remodelling to support GLUT4 translocation. |
