Model of interaction between GASP1 and Myostatin.

<p>(after Lee, 2004) A) Myostatin signalling through ActRIIB receptor is crucial for the regulation of muscle growth. Myostatin is synthesized as a precursor protein (pro-myostatin) that undergoes proteolytic processing (furin cleavage) to generate an N-terminal propeptide and a disulfide-linked C-terminal dimer, which is the biologically active molecule. Myostatin is in circulation as an inactive latent complex (propeptide and mature myostatin) which is activated by BMP/Tolloid family of metalloproteinases. Active myostatin, mostly binds to the ActRIIB receptor and engages the signalling cascade leading to the inhibition of myoblast differentiation and proliferation. B) Specific inhibitors can prevent binding of myostatin to ActRIIB. One of them is GASP1 which also binds to the propeptide. We hypothezise that GASP1 could interact with the inactive latent complex preventing propeptide cleavage by BMP/Tolloid through antiprotease activity of the second kunitz domain.