The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300

Genomics. 2002 Nov;80(5):473-81.

Abstract

Nesprin-1 and nesprin-2 (also known as Syne-1 and Syne-2,) are large ( approximately 3300-residue) vertebrate proteins associated with emerin and lamin A at the nuclear envelope of muscle cells and other cell types. We show that the previously described nesprins are short isoforms of giant proteins comprising an actin-binding amino-terminus connected to a carboxy-terminal klarsicht-related transmembrane domain by a massive ( approximately 6000-8000 amino acid) spectrin-like rod domain, making full-length nesprin-1, at one megadalton, the largest non-titin protein hitherto described in humans. We find that MSP-300, a 7000-residue Drosophila melanogaster protein whose disruption results in defects of muscle development, corresponds to the N-terminal two-thirds of the Drosophila nesprin ortholog. A nesprin-like protein is also encoded by the nematode genome. Moreover, we demonstrate that the larger isoforms of nesprin-1, like MSP-300, are localized to the sarcomeric Z-line of both skeletal and cardiac muscle. The recognition that a characteristic muscle-specific mutant phenotype in the fly results from a disruption of its nesprin ortholog reinforces the candidacy of the human proteins for involvement in genetic diseases of skeletal and cardiac muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytoskeletal Proteins
  • Drosophila Proteins*
  • Drosophila melanogaster / cytology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Multigene Family
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Nematoda
  • Nerve Tissue Proteins*
  • Nuclear Proteins*
  • Phylogeny
  • Protein Isoforms
  • Sequence Alignment
  • Subcellular Fractions

Substances

  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Msp300 protein, Drosophila
  • Muscle Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • SYNE1 protein, human
  • SYNE2 protein, human

Associated data

  • GENBANK/AF495910
  • GENBANK/AF495911
  • GENBANK/AF495912
  • GENBANK/AF521597
  • GENBANK/AF521598
  • GENBANK/AY126454