Expression and stability of myelin-associated elements
1University of Oulu, Faculty of Medicine, Department of Anatomy and Cell Biology
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|Persistent link:|| http://urn.fi/urn:isbn:9789514285714
|Publish Date:|| 2007-09-25
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium A101 of the Department of Anatomy and Cell Biology, on October 5th, 2007, at 12 noon
Ph. D. Richard H. Quarles
Ph. D. Åsa Fex Svenningsen
The function of the nervous system is based on the targeted transmission of electrical impulses assuring the coordinated function of tissues and organs. Myelination of the neuronal axons allows the fast saltatory conduction by producing repetitive sites where sodium channels cluster on the axolemma. In the peripheral nervous system (PNS), myelin is formed by differentiation of the Schwann cell plasma membrane. The cells form myelin by first wrapping consecutive layers of the plasma membrane around the axons and then excluding almost all of the cytoplasm from the structure, forming compacted and non-compacted membrane compartments.
The myelin-associated glycoprotein (MAG) is located in all of the non-compacted regions of the PNS myelin sheath. Its two isoforms, L-MAG and S-MAG, differ only by the carboxy-terminal tails of their respective cytoplasmic domains. Both of the MAG isoforms are found in PNS myelin. They are differentially expressed during development and, until now, it has been thought that L-MAG is not present in the mature PNS myelin sheaths of murines. This study shows that both MAG isoforms can be found in different non-compacted membrane compartments in the mature PNS myelin sheaths in dorsal root ganglia (DRG)/Schwann cell cocultures.
Early myelin development and myelin maturation were analyzed by means of a study of the expression of two early myelin markers, MAG and galactosyl cerebrosides (Gal-CB), believed to play roles in both myelin formation and maintenance. In order to allow the exploitation of the full potential of the DRG/Schwann cell coculture model through the use of mouse mutants, a coculture method was developed in which mouse DRGs and Schwann cells are able, for the first time, to produce significant amounts of myelin. To further explore the role of MAG in myelin maintenance and stability, the stability of purified MAG was studied through extensive degradation experiments.
Acta Universitatis Ouluensis. D, Medica
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