title: Syndecan-4 and beta1 integrin are regulated by electrical activity in skeletal muscle: Implications for cell adhesion.
abstract: Syndecan-4 and integrins are involved in the cell migration and adhesion processes in several cell types. Syndecan-4, a transmembrane heparan sulfate proteoglycan, is associated to focal adhesions in adherent cells and has been described as a marker of satellite cells in skeletal muscle. In this tissue, beta1 integrin forms heterodimers with alpha5 and alpha6 during myoblast differentiation and with alpha7 in adult muscle. Here, we show that the levels of these two cell surface membrane molecules are regulated by spontaneous electrical activity during the differentiation of rat primary myoblasts. Syndecan-4 and beta1 integrin protein levels decrease after the inhibition of electrical activity using tetrodotoxin (TTX). Syndecan-4 also decreases substantially in denervated rat tibialis anterior muscle. Indirect immunofluorescence analysis shows that syndecan-4 and beta1 integrin co-localize with vinculin, a molecular marker of costameres in skeletal muscle myofibers. Co-localization is lost in inactive myotubes adopting a diffuse pattern, suggesting that the costameric organization is disrupted in TTX-treated myotubes. Moreover, the inhibition of spontaneous electrical activity decreases myotube cell adhesion. In summary, this work shows that syndecan-4 and beta1 integrin protein levels and their localization in costameric structures are regulated by electrical activity and suggests that this regulatory mechanism influences the adhesion properties of skeletal myotubes during differentiation.
authors.affiliation: Centro de Regulación Celular y Patología, Centro de Regeneración y Envejecimiento, Departamento de Biología Celular y Molecular, Millenium Institute for Fundamental and Applied Biology, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Ugarte
authors.forename: Cristian
authors.initials: C
authors.lastname: Santander
authors.forename: Enrique
authors.initials: E
authors.lastname: Brandan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019012:Integrin beta1 / Q000502:physiology*; D008297:Male; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000502:physiology*; D032446:Myoblasts / Q000502:physiology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026941:Sodium Channel Blockers / Q000494:pharmacology; D053671:Syndecan-4 / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D019012:Integrin beta1; D026941:Sodium Channel Blockers; D053671:Syndecan-4; D013779:Tetrodotoxin; D012313:RNA