Elsevier

Molecular Metabolism

Volume 42, December 2020, 101091
Molecular Metabolism

Original Article
β-catenin regulates muscle glucose transport via actin remodelling and M-cadherin binding

https://doi.org/10.1016/j.molmet.2020.101091Get rights and content
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open access

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.

Abstract

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.

Keywords

Beta-catenin
Actin-remodelling
Glucose transport
M-cadherin
GLUT4 trafficking

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