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Published online
doi:10.1083/jcb.200808034
The Journal of Cell Biology, Vol. 183, No. 5, 909-921
The Rockefeller University Press, 0021-9525 $30.00
© Devaux et al.
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Article

Tight junctions potentiate the insulative properties of small CNS myelinated axons



Jerome Devaux1,2 and Alexander Gow3,4,5

1 Département Signalisation Neuronale, Le Centre de Recherche de Neurobiologie-Neurophysiologie de Marseille, Unités Mixtes de Recherche 6231, Centre National de la Recherche Scientifique, Université de la Méditerranée, Université Paul Cézanne, Institut Fédératif de Recherche Jean Roche, 13916, Marseille, Cedex 20, France
2 Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA 19104
3 Center for Molecular Medicine and Genetics, 4 Carman and Ann Adams Department of Pediatrics, and 5 Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201

Correspondence to Alexander Gow: agow{at}med.wayne.edu

Claudin family proteins form the physical barriers of tight junctions (TJs) and regulate paracellular diffusion across polarized epithelia. In addition to these heterotypic TJs, claudin 11 forms autotypic TJs comprising the radial component of central nervous system myelin. The exact function of these TJs has been unclear, although their location at the membrane perimeter is well sited to regulate diffusion between the interstitium and intramyelinic space. In this study, we demonstrate that claudin 11 affords rapid nerve conduction principally for small diameter myelinated axons. Claudin 11–null mice have preserved myelin and axonal architecture, but as much as a 60% decrease in conduction. They also have increased action potential thresholds and activated internodal potassium channels. These data indicate that TJs modulate the biophysical properties of myelin. Computational modeling reveals that claudin 11 reduces current flow through myelin and moderates its capacitive charging. Together, our data shed new light on myelin structural components and our understanding of the biology and pathophysiology of this membrane.

Abbreviations used in this paper: 4-AP, 4-aminopyridine; ACSF, artificial cerebrospinal fluid; AP, action potential; CAP, compound AP; CNS, central nervous system; CV, conduction velocity; DCM, double-cable model; DTX, dendrotoxin-1; MS, multiple sclerosis; PNS, peripheral nervous system; SHK, Stichodactyla helianthus toxin; TJ, tight junction; TJM, TJ model.

© 2008 Devaux and Gow This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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