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Gai2 Signaling Promotes Skeletal Muscle Hypertrophy, Myoblast Differentiation, and Muscle Regeneration

Minetti, Giulia and Rosenstiel, Antonia and Werner, Annick and Meier, Viktor and Kahle, Peter and Glass, David and Feige, Jerome and Fornaro, Mara and Bombard, Florian and Sailer, Andreas and Bassilana, Frederic and Lambert, Christian (2011) Gai2 Signaling Promotes Skeletal Muscle Hypertrophy, Myoblast Differentiation, and Muscle Regeneration. Science Signaling, 4 (201). ra8. ISSN 1945-0877

Abstract

Skeletal muscle atrophy results in loss of strength and an increased risk of mortality. We found that lysophosphatidic
acid, which activates a G protein (heterotrimeric guanine nucleotide–binding protein)–
coupled receptor, stimulated skeletal muscle hypertrophy through activation of Gai2. Expression of a
constitutively active mutant of Gai2 stimulated myotube growth and differentiation, effects that required
the transcription factor NFAT (nuclear factor of activated T cells) and protein kinase C. In addition, expression
of the constitutively active Gai2 mutant inhibited atrophy caused by the cachectic cytokine TNFa (tumor
necrosis factor–a) by blocking an increase in the abundance of the mRNA encoding the E3 ubiquitin ligase
MuRF1 (muscle ring finger 1). Gai2 activation also enhanced muscle regeneration and caused a switch to
oxidative fibers. Our study thus identifies a pathway that promotes skeletal muscle hypertrophy and differentiation
and demonstrates that Gai2-induced signaling can act as a counterbalance to MuRF1-mediated
atrophy, indicating that receptors that act through Gai2 might represent potential targets for preventing
skeletal muscle wasting.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/3391

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