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Science 318 (5855): 1472-1475

Copyright © 2007 by the American Association for the Advancement of Science

Expression and Function of Junctional Adhesion Molecule-C in Myelinated Peripheral Nerves

Christoph Scheiermann,1,2 Paolo Meda,3 Michel Aurrand-Lions,4 Rime Madani,3 Yiangos Yiangou,5 Peter Coffey,6 Thomas E. Salt,6 Dominique Ducrest-Gay,3 Dorothée Caille,3 Owain Howell,7 Richard Reynolds,7 Alexander Lobrinus,3 Ralf H. Adams,8 Alan S. L. Yu,9 Praveen Anand,5 Beat A. Imhof,3* Sussan Nourshargh1,2*{dagger}

Abstract: JAM-C is an adhesion molecule that is expressed on cells within the vascular compartment and epithelial cells and, to date, has been largely studied in the context of inflammatory events. Using immunolabeling procedures in conjunction with confocal and electron microscopy, we show here that JAM-C is also expressed in peripheral nerves and that this expression is localized to Schwann cells at junctions between adjoining myelin end loops. Sciatic nerves from JAM-C–deficient [having the JAM-C gene knocked out (KO)] mice exhibited loss of integrity of the myelin sheath and defective nerve conduction as indicated by morphological and electrophysiological studies, respectively. In addition, behavioral tests showed motor abnormalities in the KO animals. JAM-C was also expressed in human sural nerves with an expression profile similar to that seen in mice. These results demonstrate that JAM-C is a component of the autotypic junctional attachments of Schwann cells and plays an important role in maintaining the integrity and function of myelinated peripheral nerves.

1 National Heart and Lung Institute, Imperial College London, London, UK.
2 William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
3 Centre Medical Universitaire (CMU), Medical Faculty, University of Geneva, Geneva, Switzerland.
4 INSERM UMR 599, Institut Paoli-Calmettes, Marseille, France.
5 Peripheral Neuropathy Unit, Division of Neurosciences and Mental Health, Imperial College London, London, UK.
6 Institute of Ophthalmology, University College London, London, UK.
7 Department of Cellular and Molecular Neuroscience, Division of Neurosciences and Mental Health, Imperial College London, London, UK.
8 London Research Institute, Cancer Research UK, London, UK.
9 Nephrology Division, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: s.nourshargh{at}qmul.ac.uk


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