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During the course of Multiple Sclerosis (MS), myelin – the membrane layer that insulates axons – is attacked by the immune system, the damage causing an interruption of nerve signal transmission. In this process, axons and oligodendrocytes, the cells that produce myelin, are also damaged. Partial myelin repair may occur. Total repair, however, requires the presence of oligodendrocytes (OLGs), intact axons, and presumably molecular signals within the ECM, an elaborate structure between cells that contains signaling molecules. An important ECM constituent is laminin-2 (merosin), which is present on axons during normal physiological brain development. However, disruption of the blood-brain barrier, as occurs during MS, facilitates the deposition of serum fibronectin, another major ECM constituent, in MS lesions, raising the issue to what extent this and other matrix proteins may interfere with remyelination events. To investigate potential ECM modulation of myelination, primary oligodendrocytes (OLG) and the OLG-derived cell line OLN93 are grown on various ECM substrates in order to mimic the ECM environment of the cells at control and MS-lesion conditions. Myelin assembly is monitored by examining the intracellular flow of a model protein, the G protein of vesicular stomatitis virus (VSVG), which is specifically transported by vesicular trafficking to the myelin sheet. Our preliminary data reveal, that biosynthetic traffic to plasma membrane is significantly decreased when the cells were grown on a fibronectin substrate as compared to a laminin-2 or poly-l-lysine substrate. This work will assist in clarifying the role of integrins, the major cell membrane receptor family for ECM-cell and cell-cell contact, in regulating myelination by modulating intracellular trafficking pathways involved in myelin biogenesis.
Originele taal-2English
KwalificatieDoctor of Philosophy
  • Hoekstra, Dick, Supervisor
Datum van toekenning3-jan-0001
Plaats van publicatieGroningen
Gedrukte ISBN's9036728290
StatusPublished - 2006

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