title: Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization.
abstract: Dystroglycan is a central component of the dystrophin-glycoprotein complex implicated in the pathogenesis of several neuromuscular diseases. Although dystroglycan is expressed by Schwann cells, its normal peripheral nerve functions are unknown. Here we show that selective deletion of Schwann cell dystroglycan results in slowed nerve conduction and nodal changes including reduced sodium channel density and disorganized microvilli. Additional features of mutant mice include deficits in rotorod performance, aberrant pain responses, and abnormal myelin sheath folding. These data indicate that dystroglycan is crucial for both myelination and nodal architecture. Dystroglycan may be required for the normal maintenance of voltage-gated sodium channels at nodes of Ranvier, possibly by mediating trans interactions between Schwann cell microvilli and the nodal axolemma.
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Saito
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Rita
authors.initials: R
authors.lastname: Barresi
authors.forename: Michael D
authors.initials: MD
authors.lastname: Henry
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ross-Barta
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Cohn
authors.forename: Roger A
authors.initials: RA
authors.lastname: Williamson
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
authors.forename: Diane L
authors.initials: DL
authors.lastname: Sherman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
authors.forename: James D
authors.initials: JD
authors.lastname: Schmelzer
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Low
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D049030:Dystroglycans; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009431:Neural Conduction / Q000235:genetics; D010525:Peripheral Nerves / Q000254:growth & development* / Q000473:pathology / Q000648:ultrastructure; D011485:Protein Binding / Q000235:genetics; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D015222:Sodium Channels / Q000378:metabolism*; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D003598:Cytoskeletal Proteins; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D015222:Sodium Channels; D049030:Dystroglycans