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Molecular and Cellular Biology, November 2009, p. 5800-5812, Vol. 29, No. 21
0270-7306/09/$08.00+0     doi:10.1128/MCB.00684-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Regulation of Myoblast Differentiation by the Nuclear Envelope Protein NET39{triangledown} ,{dagger}

Guang-Hui Liu, Tinglu Guan, Kaustuv Datta, Judith Coppinger, John Yates III, and Larry Gerace*

Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037

Received 26 May 2009/ Returned for modification 5 July 2009/ Accepted 11 August 2009

Recently, several transmembrane proteins of the nuclear envelope have been implicated in regulation of signaling and gene expression. Here we demonstrate that the nuclear lamina-associated nuclear envelope transmembrane protein NET39 (Ppapdc3) functions as a negative regulator of myoblast differentiation, in part through effects on mTOR signaling. We found that NET39 is highly expressed in cardiac and skeletal muscle tissues and becomes strongly upregulated during cultured myoblast differentiation. Knockdown of NET39 by RNA interference in myoblasts strongly promoted differentiation, whereas overexpression of NET39 repressed myogenesis. Proteomic analysis of NET39 complexes immunoprecipitated from myotubes, in combination with other methods, identified mTOR as an interaction partner of NET39. We found that ectopic expression of NET39 in myoblasts negatively regulated myogenesis by diminishing mTOR activity, which in turn decreased insulin-like growth factor II production and autocrine signaling. Our results indicate that NET39 is part of the regulatory machinery for myogenesis and raise the possibility that it may be important for muscle homeostasis.

* Corresponding author. Mailing address: Department of Cell Biology, IMM-10, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 784-8514. Fax: (858) 784-0132. E-mail: lgerace{at}scripps.edu

{triangledown} Published ahead of print on 24 August 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, November 2009, p. 5800-5812, Vol. 29, No. 21
0270-7306/09/$08.00+0     doi:10.1128/MCB.00684-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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