HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 27, 18473-18481, July 7, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/27/18473    most recent M600918200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ugarte, G. Articles by Brandan, E. Search for Related Content PubMed PubMed Citation Articles by Ugarte, G. Articles by Brandan, E. Social Bookmarking                      What's this?

Transforming Growth Factor (TGF-) Signaling Is Regulated by Electrical Activity in Skeletal Muscle Cells

TGF- TYPE I RECEPTOR IS TRANSCRIPTIONALLY REGULATED BY MYOTUBE EXCITABILITY^*

From the Centro de Regulación Celular y Patología "Joaquín V. Luco", Millennium Institute for Fundamental and Applied Biology, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile

Transforming growth factor (TGF-) is involved in several cellular processes such as cell proliferation, differentiation, and apoptosis. At the cell surface, TGF- binds to serine-threonine kinase transmembrane receptors (type II and type I) to initiate Smad-dependent intracellular signaling cascades. During the early stages of skeletal muscle differentiation, myotubes start to evoke spontaneous electrical activity in association with contractions that arise following the maturation of the excitation-contraction apparatus. In this work, we report that TGF--dependent signaling is regulated by electrical activity in developing rat primary myotubes, as determined by Smad2 phosphorylation, Smad4 nuclear translocation, and p3TPLux reporter activity. This electrical activity-dependent regulation is associated with changes in TGF- type I receptor (TRI) levels, correlated with changes in transducing receptors at the cell membrane (measured through radiolabeling binding assays). The inhibition of electrical activity with tetrodotoxin, a voltage-dependent sodium channel blocker, increases TRI levels via a transcription-dependent mechanism. In contrast, the promotion of electrical activity in myotube cultures, induced by the up-regulation of voltage-dependent sodium channels or by direct stimulation with extracellular electrodes, causes TRI levels to decrease. Similar results were obtained in denervated adult muscles, suggesting that electrical activity-dependent regulation of TRI also occurs in vivo. Additional results suggest that this activity-dependent regulation is mediated by myogenin. Altogether, these findings support the possibility for a novel regulatory mechanism acting on TGF- signaling cascade in skeletal muscle cells.

Received for publication, January 30, 2006 , and in revised form, April 26, 2006.

^* This work was supported in part by Grant 13980001 from FONDAP-Biomedicine and Grant 3790 from the Muscular Dystrophy Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a postdoctoral fellowship from Millennium Institute for Fundamental and Applied Biology, financed in part by Ministerio de Planificación y Cooperación (MIDEPLAN, Chile) and by FONDAP-Biomedicine.

² Supported in part by an International Research Scholar grant from the Howard Hughes Medical Institute. To whom correspondence should be addressed: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, MIFAB, P. Universidad Católica de Chile, Casilla 114-D, Santiago, Chile. Fax: 56-2-635-5395; E-mail: ebrandan{at}bio.puc.cl.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. D. Kollias and J. C. McDermott Transforming growth factor-{beta} and myostatin signaling in skeletal muscle J Appl Physiol, March 1, 2008; 104(3): 579 - 587. [Abstract] [Full Text] [PDF]

				R. Martinez-Marmol, M. David, R. Sanches, M. Roura-Ferrer, N. Villalonga, E. Sorianello, S. M. Webb, A. Zorzano, A. Guma, C. Valenzuela, et al. Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair Cardiovasc Res, December 1, 2007; 76(3): 430 - 441. [Abstract] [Full Text] [PDF]

				H. Tang and D. Goldman Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade PNAS, November 7, 2006; 103(45): 16977 - 16982. [Abstract] [Full Text] [PDF]