Unique Role of Dystroglycan in Peripheral Nerve Myelination, Nodal Structure, and Sodium Channel Stabilization

• Published in: Neuron (Cambridge, Mass.) Vol. 38; no. 5; pp. 747 - 758
• Main Authors: Saito, Fumiaki, Moore, Steven A, Barresi, Rita, Henry, Michael D, Messing, Albee, Ross-Barta, Susan E, Cohn, Ronald D, Williamson, Roger A, Sluka, Kathleen A, Sherman, Diane L, Brophy, Peter J, Schmelzer, James D, Low, Phillip A, Wrabetz, Lawrence, Feltri, M.Laura, Campbell, Kevin P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.06.2003; Elsevier Limited
• Subjects: Ablation; Animals; Animals, Newborn; Cell Membrane - metabolism; Cell Membrane - pathology; Cell Membrane - ultrastructure; Cells, Cultured; Clonal deletion; Colleges & universities; Cytoskeletal Proteins - deficiency; Cytoskeletal Proteins - genetics; Dystroglycan; Dystroglycans; Dystrophin; Laminin - genetics; Laminin - metabolism; Leprosy; Macromolecular Substances; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Mice; Mice, Knockout; Microscopy; Movement Disorders - genetics; Movement Disorders - metabolism; Movement Disorders - physiopathology; Muscular dystrophy; Muscular system; Musculoskeletal system; Mutation - genetics; Myelin Sheath - metabolism; Myelin Sheath - pathology; Myelin Sheath - ultrastructure; Myelination; Nerve conduction; Neural Conduction - genetics; Neuromuscular diseases; Nodes of Ranvier; Peripheral nerves; Peripheral Nerves - growth & development; Peripheral Nerves - pathology; Peripheral Nerves - ultrastructure; Peripheral neuropathy; Protein Binding - genetics; Proteins; Ranvier's Nodes - metabolism; Ranvier's Nodes - pathology; Ranvier's Nodes - ultrastructure; Rodents; Schwann cells; Schwann Cells - metabolism; Schwann Cells - ultrastructure; Sodium channels (voltage-gated); Sodium Channels - metabolism; Wallerian Degeneration - genetics; Wallerian Degeneration - metabolism; Wallerian Degeneration - physiopathology; Non-programmatic
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(03)00301-5

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.