Regulation of myoblast differentiation by the nuclear envelope protein NET39

Mol Cell Biol. 2009 Nov;29(21):5800-12. doi: 10.1128/MCB.00684-09. Epub 2009 Aug 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation*
  • Humans
  • Insulin-Like Growth Factor II / biosynthesis
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Muscle Development
  • Muscle, Striated / metabolism
  • Myoblasts / cytology*
  • Myoblasts / metabolism*
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Kinases / metabolism
  • Proteomics
  • TOR Serine-Threonine Kinases

Substances

  • Membrane Proteins
  • Net39 protein, mouse
  • Nuclear Proteins
  • Insulin-Like Growth Factor II
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse