title: Laminin binds to myostatin and attenuates its signaling.
abstract: Myostatin is a growth and differentiation factor and acts as a negative regulator of skeletal muscle mass. Although the mechanism whereby myostatin controls muscle cell growth is mostly clarified, the regulation of myostatin activity after its secretion into the extracellular matrix (ECM) is still unclear. In the present study, we investigated the interaction between laminin and myostatin and the effect of laminin on myostatin signaling in vitro. The surface plasmon resonance assay showed that laminin bound to mature myostatin and activin receptor type IIB (ActRIIB), but did not bind to latency-associated protein, which remains non-covalently linked to mature myostatin. Furthermore, kinetic analysis demonstrated that the affinity of mature myostatin for laminin was similar to that for ActRIIB. Next, we examined the action of laminin on the myostatin signaling pathway using a conventional reporter assay. The luciferase activity of myostatin-treated cells was repressed significantly (P < 0.05) by coincubation of laminin. These results suggest that laminin has a potential to regulate myostatin activity through binding to mature myostatin and/or its receptor ActRIIB.
authors.affiliation: Meat Science Laboratory, Division of Bioresources and Bioproduction, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Yasaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kishioka
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Wakamatsu
authors.forename: Takanori
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D002478:Cells, Cultured; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D008840:Microfilament Proteins / Q000378:metabolism; D055435:Myostatin / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C107063:ACTRT1 protein, human; D007797:Laminin; D008840:Microfilament Proteins; D055435:Myostatin
keywords: ActRIIB; laminin; myostatin; signaling; skeletal muscle