Premium
Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition
Author(s) -
KellerPinter Aniko,
Szabo Kitti,
Kocsis Tamas,
Deak Ferenc,
Ocsovszki Imre,
Zvara Agnes,
Puskas Laszlo,
Szilak Laszlo,
Dux Laszlo
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13227
Subject(s) - myostatin , syndecan 1 , microbiology and biotechnology , chemistry , signalling , transition (genetics) , biology , cell , biochemistry , gene
Myostatin, a TGF ‐β superfamily member, is a negative regulator of muscle growth. Here we describe how myostatin activity is regulated by syndecan‐4, a ubiquitous transmembrane heparan sulfate proteoglycan. During muscle regeneration the levels of both syndecan‐4 and promyostatin decline gradually after a sharp increase, concurrently with the release of mature myostatin. Promyostatin and syndecan‐4 co‐immunoprecipitate, and the interaction is heparinase‐sensitive. Sh RNA ‐mediated silencing of syndecan‐4 reduces C2C12 myoblast proliferation via blocking the progression from G1‐ to S‐phase of the cell cycle, which is accompanied by elevated levels of myostatin and p21(Waf1/Cip1), and decreases in cyclin E and cyclin D1 expression. Our results suggest that syndecan‐4 functions as a reservoir for promyostatin regulating the local bioavailability of mature myostatin.