Open AccessRegulation of Myoblast Differentiation by the Nuclear Envelope Protein NET39
Author(s) -
Guanghui Liu,
Tinglu Guan,
Kaustuv Datta,
Judith A. Coppinger,
John R. Yates,
Larry Gerace
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00684-09
Subject(s) - myogenesis , biology , myocyte , c2c12 , microbiology and biotechnology , nuclear lamina , gene knockdown , pi3k/akt/mtor pathway , ectopic expression , nuclear protein , signal transduction , cellular differentiation , transcription factor , gene , genetics
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-associatedn ucleare nvelopet ransmembrane 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.