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The Journal of Neuroscience, March 31, 2004, 24(13):3176-3185; doi:10.1523/JNEUROSCI.5427-03.2004

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Cellular/Molecular
Does Paranode Formation and Maintenance Require Partitioning of Neurofascin 155 into Lipid Rafts?

Dorothy P. Schafer, Rashmi Bansal, Kristian L. Hedstrom, Steven E. Pfeiffer, and Matthew N. Rasband

Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06032

Paranodal axoglial junctions in myelinated nerve fibers are essential for efficient action potential conduction and ion channel clustering. We show here that, in the mature CNS, a fraction of the oligodendroglial 155 kDa isoform of neurofascin (NF-155), a major constituent of paranodal junctions, has key biochemical characteristics of a lipid raft-associated protein. However, despite its robust expression, NF-155 is detergent soluble before paranodes form and in purified oligodendrocyte cell cultures. Only during its progressive localization to paranodes is NF-155 (1) associated with detergent-insoluble complexes that float at increasingly lower densities of sucrose and (2) retained in situ after detergent treatment. Finally, mutant animals with disrupted paranodal junctions, including those lacking specific myelin lipids, have significantly reduced levels of raft-associated NF-155. Together, these results suggest that trans interactions between oligodendroglial NF-155 and axonal ligands result in cross-linking, stabilization, and formation of paranodal lipid raft assemblies.

Key words: myelin; oligodendrocyte; node of Ranvier; paranode; lipid raft; axoglial junction

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Received Dec 9, 2003; revised February 5, 2004; accepted February 10, 2004.

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