Identification and characterization of epsilon-sarcoglycans in the central nervous system

Brain Res Mol Brain Res. 2004 Jun 18;125(1-2):1-12. doi: 10.1016/j.molbrainres.2004.01.012.

Abstract

Alpha-, beta-, gamma-, and delta-sarcoglycans (SGs) are transmembrane glycoprotein components of the dystrophin-associated protein (DAP) complex, which is critical for the stability of the striated muscle cell membrane. Epsilon-SG was found as a homologue of alpha-SG, but unlike other SG members, it is ubiquitously expressed in various tissues as well as in striated muscle. Moreover, mutations in the epsilon-SG gene cause myoclonus-dystonia, indicating the importance of epsilon-SG for the function in the central nervous system. To gain insight into the role of epsilon-SG, its expression and subcellular distribution in mouse tissues and especially in the mouse brain were investigated. Analysis by reverse transcription-polymerase chain reaction showed four splice variants of epsilon-SG transcripts in the mouse brain, two of which are major transcript forms. One is a conventional form including exon 8 (epsilon-SG1), and the other is a novel form excluding exon 8 but including a previously unknown exon, 11b (epsilon-SG2). Immunoblot analysis using various mouse tissues indicated a broad expression pattern for epsilon-SG1, but epsilon-SG2 was expressed exclusively in the brain. Therefore, both epsilon-SG isoforms coexist in various regions of the brain. Furthermore, these isoforms were found in neuronal cells using immunohistochemical analysis. Subcellular fractionation of brain homogenates, however, indicated that epsilon-SG1 and epsilon-SG2 are relatively enriched in post- and pre-synaptic membrane fractions, respectively. These results suggest that the two epsilon-SG isoforms might play different roles in synaptic functions of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / cytology
  • Brain / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Central Nervous System / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sarcoglycans
  • Subcellular Fractions / metabolism
  • Synapses / physiology
  • Tissue Distribution

Substances

  • Cytoskeletal Proteins
  • Membrane Glycoproteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Sarcoglycans

Associated data

  • GENBANK/AB117974
  • GENBANK/AB117975