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Article
Subject Categories: Membranes & Transport | Neuroscience
The EMBO Journal (2006) 25, 5037–5048, doi:10.1038/sj.emboj.7601376
Published online 12 October 2006
Myelin basic protein-dependent plasma membrane reorganization in the formation of myelin
Dirk Fitzner1, 2, Anja Schneider1, 2, Angelika Kippert1, 2, Wiebke Möbius2, Katrin I Willig3, Stefan W Hell3, Gertrude Bunt2, Katharina Gaus4 and Mikael Simons1, 2
1 Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, Göttingen, Germany
2 Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
3 Department of NanoBiophotonics, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany
4 Centre for Vascular Research at the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

To whom correspondence should be addressed
Mikael Simons, Centre for Biochemistry and Molecular Cell Biology, Max-Planck Institute for Experimental Medicine, University of Göttingen, Hermann Rein Str. 3, 37073 Göttingen, Germany. Tel.: +49 551 3899533; Fax: +49 551 3899201; E-mail: msimons@gwdg.de

Received 5 May 2006; Accepted 11 September 2006; Published online 12 October 2006.
Abstract
During vertebrate development, oligodendrocytes wrap their plasma membrane around axons to produce myelin, a specialized membrane highly enriched in galactosylceramide (GalC) and cholesterol. Here, we studied the formation of myelin membrane sheets in a neuron–glia co-culture system. We applied different microscopy techniques to visualize lipid packing and dynamics in the oligodendroglial plasma membrane. We used the fluorescent dye Laurdan to examine the lipid order with two-photon microscopy and observed that neurons induce a dramatic lipid condensation of the oligodendroglial membrane. On a nanoscale resolution, using stimulated emission depletion and fluorescence resonance energy transfer microscopy, we demonstrated a neuronal-dependent clustering of GalC in oligodendrocytes. Most importantly these changes in lipid organization of the oligodendroglial plasma membrane were not observed in shiverer mice that do not express the myelin basic protein. Our data demonstrate that neurons induce the condensation of the myelin-forming bilayer in oligodendrocytes and that MBP is involved in this process of plasma membrane rearrangement. We propose that this mechanism is essential for myelin to perform its insulating function during nerve conduction.
Keywords: membrane condensation, myelin, myelin basic protein, neurons, oligodendrocytes
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