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

J. Biol. Chem., Vol. 283, Issue 15, 10208-10220, April 11, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/15/10208    most recent M710604200v1 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ariga, M. Articles by Kanzaki, M. Search for Related Content PubMed PubMed Citation Articles by Ariga, M. Articles by Kanzaki, M. Social Bookmarking                      What's this?

Functional Role of Sortilin in Myogenesis and Development of Insulin-responsive Glucose Transport System in C2C12 Myocytes^*

Miyako Ariga^¶1, Taku Nedachi, Hideki Katagiri^¶, and Makoto Kanzaki²

From the 21st Century COE program Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8575, the Division of Biomaterials, Biomedical Engineering Research Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, and the ^¶Division of Advanced Therapeutics for Metabolic Diseases, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Sortilin has been implicated in the formation of insulin-responsive GLUT4 storage vesicles in adipocytes by regulating sorting events between the trans-Golgi-network and endosomes. We herein show that sortilin serves as a potent myogenic differentiation stimulator for C2C12 myocytes by cooperatively functioning with p75NTR, which subsequently further contributes to development of the insulin-responsive glucose transport system in C2C12 myotubes. Sortilin expression was up-regulated upon C2C12 differentiation, and overexpression of sortilin in C2C12 cells significantly stimulated myogenic differentiation, a response that was completely abolished by either anti-p75NTR- or anti-nerve growth factor (NGF)-neutralizing antibodies. Importantly, small interference RNA-mediated suppression of endogenous sortilin significantly inhibited C2C12 differentiation, indicating the physiological significance of sortilin expression in the process of myogenesis. Although sortilin overexpression in C2C12 myotubes improved insulin-induced 2-deoxyglucose uptake, as previously reported, this effect apparently resulted from a decrease in the cellular content of GLUT1 and an increase in GLUT4 via differentiation-dependent alterations at both the gene transcriptional and the post-translational level. In addition, cellular contents of Ubc9 and SUMO-modified proteins appeared to be increased by sortilin overexpression. Taken together, these data demonstrate that sortilin is involved not only in development of the insulin-responsive glucose transport system in myocytes, but is also directly involved in muscle differentiation via modulation of proNGF-p75NTR.

Received for publication, December 31, 2007

^* This work was supported in part by grants from the New Energy and Industrial Technology Development Organization and the Ministry of Education, Science, Sports and Culture of Japan. 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 Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

² Supported by Special Coordinated Funds for Promoting Science and Technology. To whom correspondence should be addressed: Tel.: 81-22-717-7581; Fax: 81-22-717-7578; E-mail: kanzakimakoto{at}mac.com.

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

This article has been cited by other articles:

				J. Shi, G. Huang, and K. V. Kandror Self-assembly of Glut4 Storage Vesicles during Differentiation of 3T3-L1 Adipocytes J. Biol. Chem., October 31, 2008; 283(44): 30311 - 30321. [Abstract] [Full Text] [PDF]