Laminin binds to myostatin and attenuates its signaling

摘要

Myostatin is a growth and differentiation factor and acts as a negative regulator of skeletal muscle mass. Although themechanism whereby myostatin controls muscle cell growth is mostly clarified, the regulation of myostatin activity after itssecretion into the extracellular matrix (ECM) is still unclear. In the present study, we investigated the interaction betweenlaminin and myostatin and the effect of laminin on myostatin signaling in vitro. The surface plasmon resonance assayshowed that laminin bound to mature myostatin and activin receptor type IIB (ActRIIB), but did not bind to latencyassociatedprotein, which remains non-covalently linked to mature myostatin. Furthermore, kinetic analysis demonstratedthat the affinity of mature myostatin for laminin was similar to that for ActRIIB. Next, we examined the action of lamininon the myostatin signaling pathway using a conventional reporter assay. The luciferase activity of myostatin-treated cellswas repressed significantly (P < 0.05) by coincubation of laminin. These results suggest that laminin has a potential toregulate myostatin activity through binding to mature myostatin and/or its receptor ActRIIB.