Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A.

Proceedings of the National Academy of Sciences of the United States of America
Se-Jin LeeThomas A Rando

Abstract

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the resul...Continue Reading

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Citations

Dec 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sandeep Ravindran
May 4, 2021·The Journal of Clinical Investigation·Se-Jin Lee
Jun 2, 2021·The Journal of Clinical Investigation·Francesca SolagnaTobias B Huber
Aug 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yewei LiuSe-Jin Lee
Sep 17, 2021·Scientific Reports·Ravindra KumarRoselyne Castonguay

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Methods Mentioned

BETA
X-ray
antisense oligonucleotide
enzyme-linked immunosorbent assay

Software Mentioned

Volocity

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