Decorin binds myostatin and modulates its activity to muscle cells.
Myostatin, a member of TGF-beta superfamily of growth factors, acts as a negative regulator of skeletal muscle mass. The mechanism whereby myostatin controls the proliferation and differentiation of myogenic cells is mostly clarified. However, the regulation of myostatin activity to myogenic cells after its secretion in the extracellular matrix (ECM) is still unknown. Decorin, a small leucine-rich proteoglycan, binds TGF-beta and regulates its activity in the ECM. Thus, we hypothesized that decorin could also bind to myostatin and participate in modulation of its activity to myogenic cells. In order to test the hypothesis, we investigated the interaction between myostatin and decorin by surface plasmon assay. Decorin interacted with mature myostatin in the presence of concentrations of Zn(2+) greater than 10microM, but not in the absence of Zn(2+). Kinetic analysis with a 1:1 binding model resulted in dissociation constants (K(D)) of 2.02x10(-8)M and 9.36x10(-9)M for decorin and the core protein of decorin, respectively. Removal of the glycosaminoglycan chain by chondroitinase ABC digestion did not affect binding, suggesting that decorin could bind to myostatin with its core protein. Furthermore, we demonstrated that immobilized decorin could rescue the inhibitory effect of myostatin on myoblast proliferation in vitro. These results suggest that decorin could trap myostatin and modulate its activity to myogenic cells in the ECM.
Miura
Takayuki
T
Meat Science Laboratory, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
Kishioka
Yasuhiro
Y
Wakamatsu
Jun-ichi
J
Hattori
Akihito
A
Hennebry
Alex
A
Berry
Carole J
CJ
Sharma
Mridula
M
Kambadur
Ravi
R
Nishimura
Takanori
T
D000818:Animals; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D055435:Myostatin; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism* / Q000502:physiology; D020349:Surface Plasmon Resonance; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015032:Zinc
C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; C525912:Mstn protein, mouse; D055435:Myostatin; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D015032:Zinc