Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis

Nature Communications
Sonia Rodríguez-FdezXosé R Bustelo

Abstract

Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase pathway in that tissue. Consistent with this, mice bearing a Vav2 protein with decreased catalytic activity exhibit reduced muscle mass, lack of proper insulin responsiveness and, at much later times, a metabolic syndrome-like condition. Conversely, mice expressing a catalytically hyperactive Vav2 develop muscle hypertrophy and increased insulin responsiveness. Of note, while hypoactive Vav2 predisposes to, hyperactive Vav2 protects against high fat diet-induced metabolic imbalance. These data unveil a regulatory layer affecting the signaling output of insulin family factors in muscle.

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Citations

May 1, 2021·Cells·Polly A MachinHeidi C E Welch
Jul 16, 2021·Chemico-biological Interactions·David Hernandez-Toledano, Libia Vega

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Methods Mentioned

BETA
GTPases
nucleotide exchange
nuclear magnetic resonance
PCR
immunoprecipitation
GTPase
FACS
electrophoresis
flow cytometry
ELISA

Software Mentioned

ImageJ Manager
ImageJ “ Analyze Particles
LAS AF
StepOne
GraphPad Prism
ImageJ

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