Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves.
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.
National Heart and Lung Institute, Imperial College London, London, UK.
Christoph
C
Scheiermann
Paolo
P
Meda
Michel
M
Aurrand-Lions
Rime
R
Madani
Yiangos
Y
Yiangou
Peter
P
Coffey
Thomas E
TE
Salt
Dominique
D
Ducrest-Gay
Dorothée
D
Caille
Owain
O
Howell
Richard
R
Reynolds
Alexander
A
Lobrinus
Ralf H
RH
Adams
Alan S L
AS
Yu
Praveen
P
Anand
Beat A
BA
Imhof
Sussan
S
Nourshargh
D000200:Action Potentials; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000378:metabolism* / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D013497:Sural Nerve / Q000378:metabolism / Q000502:physiology
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C486723:Jam3 protein, mouse; D008565:Membrane Proteins