A model for CMT disease: Proteomic analysis of optic nerve lipid rafts reveals new paranodal proteins

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J Neurosci Res. 2009 Jan 20. [Epub ahead of print]

Proteomic analysis of optic nerve lipid rafts reveals new paranodal

proteins.

Ogawa Y, Rasband MN.

Department of Neuroscience, Baylor College of Medicine, Houston,

Texas.

Neuron-glia interactions at paranodal junctions play important roles

in action potential propagation. Among their many functions, they

contribute to the passive electrical properties of myelinated nerve

fibers and actively regulate the polarized distribution of ion

channels along axons.

Despite their importance, relatively little is known about the

molecules responsible for paranode formation and function. Paranodal

junction formation apparently depends on interactions among three

cell adhesion molecules: caspr and contactin on the axon and

neurofascin 155 (NF-155) on the glial membrane.

Using Caspr-null paranodal mutant mice, we demonstrate that loss of

paranodal junctions causes failure of NF-155 to partition into lipid

rafts, indicating that proteins located at paranodal junctions have

biochemical characteristics of lipid raft-associated proteins.

Based on this property of paranodal junctions, mass spectrometry of

lipid rafts isolated from a pure white matter tract (optic nerve) was

used to search for new paranodal proteins. Because we used a

relatively crude biochemical preparation, we identified several

hundred different proteins. Among these, we found all previously

described paranodal proteins.

Further analysis based on antibody staining of central and peripheral

nerves revealed beta-adducin, septin 2, and sh3p8 as putative

paranodal proteins. We describe the localization of these proteins in

relation to other markers of nodes, paranodes, and juxtaparanodes in

adult and developing nerve fibers.

Finally, we describe their distribution in dysmyelinating TremblerJ

mice, a model for the peripheral neuropathy Charcot-Marie-Tooth

disease.