Identification of a novel muscle A-type lamin-interacting protein (MLIP)

J Biol Chem. 2011 Jun 3;286(22):19702-13. doi: 10.1074/jbc.M110.165548. Epub 2011 Apr 15.

Abstract

Mutations in the A-type lamin (LMNA) gene are associated with age-associated degenerative disorders of mesenchymal tissues, such as dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and limb-girdle muscular dystrophy. The molecular mechanisms that connect mutations in LMNA with different human diseases are poorly understood. Here, we report the identification of a Muscle-enriched A-type Lamin-interacting Protein, MLIP (C6orf142 and 2310046A06rik), a unique single copy gene that is an innovation of amniotes (reptiles, birds, and mammals). MLIP encodes alternatively spliced variants (23-57 kDa) and possesses several novel structural motifs not found in other proteins. MLIP is expressed ubiquitously and most abundantly in heart, skeletal, and smooth muscle. MLIP interacts directly and co-localizes with lamin A and C in the nuclear envelope. MLIP also co-localizes with promyelocytic leukemia (PML) bodies within the nucleus. PML, like MLIP, is only found in amniotes, suggesting that a functional link between the nuclear envelope and PML bodies may exist through MLIP. Down-regulation of lamin A/C expression by shRNA results in the up-regulation and mislocalization of MLIP. Given that MLIP is expressed most highly in striated and smooth muscle, it is likely to contribute to the mesenchymal phenotypes of laminopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / physiology*
  • Animals
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Co-Repressor Proteins
  • Gene Expression Regulation / physiology*
  • Humans
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Mice
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / genetics
  • Muscles / cytology
  • Muscles / metabolism*
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organ Specificity
  • Promyelocytic Leukemia Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Carrier Proteins
  • Co-Repressor Proteins
  • Lamin Type A
  • MLIP protein, mouse
  • Muscle Proteins
  • Nuclear Proteins
  • Pml protein, mouse
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins