A role for Regulator of G protein Signaling-12 (RGS12) in the balance between myoblast proliferation and differentiation

Adam B. Schroer, Junaith Mohamed, Melinda D. Willard, Vincent Setola, Emily Oestreich, David P. Siderovski

Research output: Contribution to journalArticle

Abstract

Regulators of G Protein Signaling (RGS proteins) inhibit G protein-coupled receptor (GPCR) signaling by accelerating the GTP hydrolysis rate of activated Gα subunits. Some RGS proteins exert additional signal modulatory functions, and RGS12 is one such protein, with five additional, functional domains: a PDZ domain, a phosphotyrosine-binding domain, two Ras-binding domains, and a GαGDP-binding GoLoco motif. RGS12 expression is temporospatially regulated in developing mouse embryos, with notable expression in somites and developing skeletal muscle. We therefore examined whether RGS12 is involved in the skeletal muscle myogenic program. In the adult mouse, RGS12 is expressed in the tibialis anterior (TA) muscle, and its expression is increased early after cardiotoxin-induced injury, suggesting a role in muscle regeneration. Consistent with a potential role in coordinating myogenic signals, RGS12 is also expressed in primary myoblasts; as these cells undergo differentiation and fusion into myotubes, RGS12 protein abundance is reduced. Myoblasts isolated from mice lacking Rgs12 expression have an impaired ability to differentiate into myotubes ex vivo, suggesting that RGS12 may play a role as a modulator/switch for differentiation. We also assessed the muscle regenerative capacity of mice conditionally deficient in skeletal muscle Rgs12 expression (via Pax7-driven Cre recombinase expression), following cardiotoxin-induced damage to the TA muscle. Eight days post-damage, mice lacking RGS12 in skeletal muscle had attenuated repair of muscle fibers. However, when mice lacking skeletal muscle expression of Rgs12 were cross-bred with mdx mice (a model of human Duchenne muscular dystrophy), no increase in muscle degeneration was observed over time. These data support the hypothesis that RGS12 plays a role in coordinating signals during the myogenic program in select circumstances, but loss of the protein may be compensated for within model syndromes of prolonged bouts of muscle damage and repair.

Original languageEnglish (US)
Article numbere0216167
JournalPloS one
Volume14
Issue number8
DOIs
StatePublished - Jan 1 2019

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GTP-Binding Protein Regulators
myoblasts
Myoblasts
G-proteins
Muscle
Muscles
Skeletal Muscle
skeletal muscle
Cardiotoxins
mice
muscles
Skeletal Muscle Fibers
RGS Proteins
Inbred mdx Mouse
PDZ Domains
Repair
Somites
Phosphotyrosine
Duchenne Muscular Dystrophy
Cell Fusion

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A role for Regulator of G protein Signaling-12 (RGS12) in the balance between myoblast proliferation and differentiation. / Schroer, Adam B.; Mohamed, Junaith; Willard, Melinda D.; Setola, Vincent; Oestreich, Emily; Siderovski, David P.

In: PloS one, Vol. 14, No. 8, e0216167, 01.01.2019.

Research output: Contribution to journalArticle

Schroer, Adam B. ; Mohamed, Junaith ; Willard, Melinda D. ; Setola, Vincent ; Oestreich, Emily ; Siderovski, David P. / A role for Regulator of G protein Signaling-12 (RGS12) in the balance between myoblast proliferation and differentiation. In: PloS one. 2019 ; Vol. 14, No. 8.
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