Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization.
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.
Saito
Fumiaki
F
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.
Moore
Steven A
SA
Barresi
Rita
R
Henry
Michael D
MD
Messing
Albee
A
Ross-Barta
Susan E
SE
Cohn
Ronald D
RD
Williamson
Roger A
RA
Sluka
Kathleen A
KA
Sherman
Diane L
DL
Brophy
Peter J
PJ
Schmelzer
James D
JD
Low
Phillip A
PA
Wrabetz
Lawrence
L
Feltri
M Laura
ML
Campbell
Kevin P
KP
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
D003598:Cytoskeletal Proteins; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D015222:Sodium Channels; D049030:Dystroglycans