Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

Aniko Keller-Pinter, Kitti Szabo, Tamas Kocsis, Ferenc Deak, Imre Ocsovszki, Agnes Zvara, Laszlo Puskas, Laszlo Szilak, Laszlo Dux

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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. ShRNA-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.

Original languageEnglish
Pages (from-to)3139-3151
Number of pages13
JournalFEBS letters
Volume592
Issue number18
DOIs
Publication statusPublished - Sep 2018

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Keywords

  • myoblast
  • myostatin
  • syndecan-4

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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