Brain, Vol. 122, No. 3, 449-460,
March 1999
© 1999 Oxford University Press
Article |
The distribution of ganglioside-like moieties in peripheral nerves
1 Departments of Neurology and 2 Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 3 National Center for Microscopy and Imaging Research at San Diego and 4 Department of Neurosciences, University of California San Diego, La Jolla, California, USA
Correspondence to:
Dr Kazim Sheikh, Department of Neurology, Johns Hopkins University, Pathology Building 509, 600 N. Wolfe Street, Baltimore, MD 21287, USA E-mail: ksheikh{at}welchlink.welch.jhu.edu
GM1 ganglioside has been implicated as a target of immune attack in some diseases of the peripheral nervous system. Anti-GM1 ganglioside antibodies are associated with certain acquired immune-mediated neuropathies. It is not clear how anti-GM1 antibodies cause nerve dysfunction and injury; however, sodium and/or potassium ion channel dysfunction at the node of Ranvier has been implicated. To gain insight into the pathogenesis of these neuropathies, we examined the distribution of GM1 ganglioside and Gal(ß13)GalNAc moieties in nerve fibres and their relationship to voltage-gated sodium and potassium (Kv1.1, 1.5) channels at the nodes of Ranvier in peripheral nerves from human, rat and dystrophic mice. Gal(ß13)GalNAc moieties were localized via the binding of cholera toxin and peanut agglutinin. As a control for the specificity of these findings, we compared the distribution of GM1 moieties to that of the ganglioside GT1b. Our study provides definitive evidence for the presence of Gal(ß13)GalNAc bearing moieties on the axolemmal surface of mature myelinated fibres and on Schwann cells. Gal(ß13)GalNAc binding sites did not have an obligatory co-localization with voltage-gated sodium channels or the potassium ion channels Kv1.1 and Kv1.5 and are thus not likely carried by these ion channels. In contrast with Gal(ß13)GalNAc, GT1b-like moieties are restricted to the axolemma.
Gal(ß13)GalNAc moieties; ani-GMI antibodies; voltage-gated sodium and potassium channels; acquired immune neuropathies; cholera toxin
CT = cholera toxin B subunit; DAB = 3,3 diaminobenzidine tetrahydrochloride; FITC = fluoroisothiocyanate; PNA = peanut agglutinin; TTC = tetanus toxin fragment C
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