Splice variation in the cytoplasmic domains of myelin oligodendrocyte glycoprotein affects its cellular localisation and transport

Louise H Boyle, James A Traherne, Gemma Plotnek, Rosemary Ward, John Trowsdale

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Although myelin oligodendrocyte glycoprotein is a candidate autoantigen in multiple sclerosis, its function remains unknown. In humans, mRNA expressed by the myelin oligodendrocyte glycoprotein gene is alternatively spliced resulting in at least nine unique protein isoforms. In this study, we investigated the sub-cellular localisation and membrane trafficking of six isoforms by cloning them into mammalian expression vectors. Confocal microscopy revealed that these protein products are expressed in different cellular compartments. While two full-length isoforms (25.6 and 25.1) are expressed at the cell surface, three alternatively spliced forms (22.7, 21.0 and 20.5) have a more intracellular distribution, localising to the endoplasmic reticulum and/or endosomes. Isoform 16.3, which lacks a transmembrane domain, is secreted. A switch in the sub-cellular localisation of myelin oligodendrocyte glycoprotein may have profound effects on receptor:ligand interactions and consequently the function of the protein. The structural features of the alternative isoforms and their differential, sub-cellular expression patterns could dictate the exposure of major immunogenic determinants within the central nervous system. Our findings highlight myelin oligodendrocyte glycoprotein splicing as a factor that could be critical to the phenotypic expression of multiple sclerosis.

Original languageEnglish
Pages (from-to)1853-1862
Number of pages10
JournalJournal of Neurochemistry
Volume102
Issue number6
DOIs
Publication statusPublished - Sep 2007
Externally publishedYes

Keywords

  • Alternative Splicing/genetics
  • Amino Acid Sequence
  • Cell Compartmentation/genetics
  • Cell Line
  • Central Nervous System/metabolism
  • Cytoplasm/metabolism
  • Endoplasmic Reticulum/metabolism
  • Endosomes/metabolism
  • Humans
  • Molecular Sequence Data
  • Multiple Sclerosis/genetics
  • Myelin Proteins
  • Myelin-Associated Glycoprotein/chemistry
  • Myelin-Oligodendrocyte Glycoprotein
  • Oligodendroglia/metabolism
  • Organelles/metabolism
  • Protein Isoforms/chemistry
  • Protein Structure, Tertiary/genetics
  • Protein Transport/physiology

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