title: A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation.
abstract: Myelinated axons are divided into four distinct regions: the node of Ranvier, paranode, juxtaparanode, and internode, each of which is characterized by a specific set of axonal proteins. Voltage-gated Na+ channels are clustered at high densities at the nodes, whereas shaker-type K+ channels are concentrated at juxtaparanodal regions. These channels are separated by the paranodal regions, where septate-like junctions are formed between the axon and the myelinating glial cells. Although oligodendrocytes and myelin sheaths are believed to play an instructive role in the local differentiation of the axon to distinct domains, the molecular mechanisms involved are poorly understood. In the present study, we have examined the distribution of axonal components in mice incapable of synthesizing sulfatide by disruption of the galactosylceramide sulfotransferase gene. These mice displayed abnormal paranodal junctions in the CNS and PNS, whereas their compact myelin was preserved. Immunohistochemical analysis demonstrated a decrease in Na+ and K+ channel clusters, altered nodal length, abnormal localization of K+ channel clusters appearing primarily in the presumptive paranodal regions, and diffuse distribution of contactin-associated protein along the internode. Similar abnormalities have been reported previously in mice lacking both galactocerebroside and sulfatide. Interestingly, although no demyelination was observed, these channel clusters decreased markedly with age. The initial timing and the number of Na+ channel clusters formed were normal during development. These results indicate a critical role for sulfatide in proper localization and maintenance of ion channels clusters, whereas they do not appear to be essential for initial cluster formation of Na+ channels.
authors.affiliation: Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dupree
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
authors.forename: Yukie
authors.initials: Y
authors.lastname: Hirahara
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.forename: Brian
authors.initials: B
authors.lastname: Popko
authors.forename: Kinuko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hitoo
authors.initials: H
authors.lastname: Nishino
authors.forename: Hiroko
authors.initials: H
authors.lastname: Baba
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal; D038983:Galactolipids; D005700:Galactosyltransferases / Q000235:genetics; D006017:Glycolipids / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism*; D051146:N-Acylsphingosine Galactosyltransferase; D010641:Phenotype; D015221:Potassium Channels / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D038983:Galactolipids; D006017:Glycolipids; D007473:Ion Channels; D046911:Macromolecular Substances; D015221:Potassium Channels; D011956:Receptors, Cell Surface; D015222:Sodium Channels; D013433:Sulfoglycosphingolipids; D005700:Galactosyltransferases; D051146:N-Acylsphingosine Galactosyltransferase; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase