β-catenin regulates muscle glucose transport via actin remodelling and M-cadherin binding
| Autor: | Brie Sorrenson, Peter R. Shepherd, Troy L. Merry, Stewart W. C. Masson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine lcsh:Internal medicine Beta-catenin Glucose transport Glucose uptake medicine.medical_treatment Actin-remodelling M-cadherin Glucose Transport Proteins Facilitative 030209 endocrinology & metabolism Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Insulin Glucose homeostasis Muscle Skeletal lcsh:RC31-1245 Molecular Biology beta Catenin Actin Mice Knockout Glucose Transporter Type 4 biology Chemistry Glucose transporter Skeletal muscle Biological Transport Cell Biology Cadherins Actins GLUT4 trafficking Cell biology Mice Inbred C57BL Protein Transport Glucose 030104 developmental biology medicine.anatomical_structure biology.protein Original Article Insulin Resistance GLUT4 Protein Binding Signal Transduction |
| Zdroj: | Molecular Metabolism, Vol 42, Iss, Pp 101091-(2020) Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | 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 β-catenin is an emerging regulator of vesicle trafficking in other tissues. Here, we investigated the involvement of β-catenin in skeletal muscle insulin-stimulated glucose transport. Methods Glucose homeostasis and transport was investigated in inducible muscle specific β-catenin knockout (BCAT-mKO) mice. The effect of β-catenin deletion and mutation of β-catenin serine 552 on signal transduction, glucose uptake and protein–protein interactions were determined in L6-G4-myc cells, and β-catenin insulin-responsive binding partners were identified via immunoprecipitation coupled to label-free proteomics. Results Skeletal muscle specific deletion of β-catenin impaired whole-body insulin sensitivity and insulin-stimulated glucose uptake into muscle independent of canonical Wnt signalling. In response to insulin, β-catenin was phosphorylated at serine 552 in an Akt-dependent manner, and in L6-G4-myc cells, mutation of β-cateninS552 impaired insulin-induced actin-polymerisation, resulting in attenuated insulin-induced glucose transport and GLUT4 translocation. β-catenin was found to interact with M-cadherin in an insulin-dependent β-cateninS552-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 β-catenin is a novel mediator of glucose transport in skeletal muscle and may contribute to insulin-induced actin-cytoskeleton remodelling to support GLUT4 translocation. Graphical abstract Image 1 Highlights • Deletion of β-catenin from the muscles of adult mice attenuates skeletal muscle glucose uptake. • Insulin stimulates phosphorylation of β-cateninS552 by a mechanism involving Akt, and this is required for insulin's effects on both GLUT4 trafficking and actin remodelling. • Insulin promotes β-catenin/M-cadherin binding, to support cortical actin remodelling associated with GLUT4 translocation. |
| Databáze: | OpenAIRE |
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