The distribution of ganglioside-like moieties in peripheral nerves.
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(beta1-3)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(beta1-3)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(beta1-3)GalNAc bearing moieties on the axolemmal surface of mature myelinated fibres and on Schwann cells. Gal(beta1-3)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(beta1-3)GalNAc, GT1b-like moieties are restricted to the axolemma.
Sheikh
K A
KA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. ksheikh@welchlink.welch.jhu.edu
Deerinck
T J
TJ
Ellisman
M H
MH
Griffin
J W
JW
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D051662:Kv1.1 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009412:Nerve Fibers / Q000378:metabolism / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000378:metabolism* / Q000648:ultrastructure; D015221:Potassium Channels / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011901:Ranvier's Nodes / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew; D015222:Sodium Channels / Q000502:physiology
D015295:Antigens, Tumor-Associated, Carbohydrate; D005732:Gangliosides; C496946:KCNA1 protein, human; C496981:KCNA5 protein, human; C496947:Kcna1 protein, mouse; C496982:Kcna5 protein, mouse; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; D051662:Kv1.1 Potassium Channel; C016467:Thomsen-Friedenreich antigen; D005677:G(M1) Ganglioside; C016481:trisialoganglioside GT1