Muscle & TGF-β signaling
The brake on muscle mass, and the antagonists that let it off.
myostatin · activin A · follistatin
Overview
Skeletal muscle mass is actively restrained. Myostatin, a member of the TGF-β superfamily, is a negative regulator: it signals through activin type II receptors and Smad2/3 to limit muscle growth. Disable it and muscle mass increases markedly.
Activin A signals through the same receptors with broader roles, and follistatin is the natural antagonist that binds and neutralizes both — raising muscle. This system is a drug-development frontier, especially for preserving muscle during the rapid weight loss seen with incretin therapies.
Key signals
TGF-β-family negative regulator of skeletal muscle mass.
Signals through activin type II receptors; muscle, fibrosis, and more.
Endogenous antagonist that neutralizes myostatin and activin.
Reference notes
- Myostatin and activin signal through activin type II receptors (ActRIIA/B) and Smad2/3 — distinct from the GPCR families.
- Follistatin is the endogenous antagonist; blocking myostatin/activin is the basis of investigational muscle-preserving therapeutics.
- This is the muscle-preservation frontier flagged by the GLP-1 weight-loss story.