Nesprin-2 is a multi-isomeric protein that binds lamin and emerin at the nuclear envelope and forms a subcellular network in skeletal muscle

J Cell Sci. 2005 Feb 15;118(Pt 4):673-87. doi: 10.1242/jcs.01642. Epub 2005 Jan 25.


Nesprin-2 is a multi-isomeric, modular protein composed of variable numbers of spectrin-repeats linked to a C-terminal transmembrane domain and/or to N-terminal paired calponin homology (CH) domains. The smaller isoforms of nesprin-2 co-localize with and bind lamin A and emerin at the inner nuclear envelope (NE). In SW-13 cells, which lack lamin A/C, nesprin-2 epitopes and emerin were both mislocalized and formed aggregates in the endoplasmic reticulum (ER). The larger isoforms and other CH-domain-containing isoforms co-localize with heterochromatin within the nucleus and are also present at the outer NE and in multiple cytoplasmic compartments. Nesprin-2 isoforms relocalize during in vitro muscle differentiation of C2C12 myoblasts to the sarcomere of myotubes. Immunogold electron microscopy using antibodies specific for three different epitopes detected nesprin-2 isoforms at multiple locations including intranuclear foci, both membranes of the NE, mitochondria, sarcomeric structures and plasma membrane foci. In adult skeletal muscle, confocal immunolocalization studies demonstrated that nesprin-2 epitopes were present at the Z-line and were also associated with the sarcoplasmic reticulum (SR) in close apposition to SERCA2. These data suggest that nesprin-2 isoforms form a linking network between organelles and the actin cytoskeleton and thus may be important for maintaining sub-cellular spatial organisation. Moreover, its association at the NE with lamin and emerin, the genes mutated in Emery-Dreifuss muscular dystrophy, suggests a mechanism to explain how disruption of the NE leads to muscle dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Alternative Splicing
  • Binding Sites
  • Cell Fractionation
  • Humans
  • Immunoprecipitation
  • Lamins / metabolism*
  • Membrane Proteins / metabolism*
  • Microfilament Proteins
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / ultrastructure
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Isoforms / analysis
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Thymopoietins / metabolism*


  • Lamins
  • Membrane Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • SYNE2 protein, human
  • Thymopoietins
  • emerin