Follistatin

Follistatin (FST) is a secreted glycoprotein rich in cysteine that works as a high-affinity ligand trap, not as a receptor blocker. A pair of follistatin molecules encircles a TGF-beta family ligand dimer and physically covers the binding faces for both type I and type II receptors, thereby neutralising activin A, myostatin and a number of BMPs.

The three isoforms

Alternative splicing plus proteolytic processing yield three forms that are commonly referenced. FST-288 has a heparan-sulfate-binding motif that anchors it to the cell surface, so it acts locally. FST-315 is the main form found in circulation. FST-344 is the initial translation product, which is processed into FST-315. A supplier listing for "follistatin-344" thus refers to the precursor construct — a point that matters in any study where tissue localisation is a variable.

What research has reported

Overexpressing follistatin in rodents was reported to increase muscle mass considerably, and follistatin gene-transfer approaches have been tested in muscular dystrophy models and in small human trials. As with direct myostatin inhibition, gains in lean mass have been reported more reliably than improvements in function. Recombinant follistatin research proteins do not survive passage through the stomach, which excludes an oral route.

Related terms and material

activin receptor · recombinant. Reference material: Follistatin-344, IGF & muscle peptides. Further reading: what is follistatin-344.