Both Laminin and Schwann Cell Dystroglycan Are Necessary for Proper Clustering of Sodium Channels at Nodes of Ranvier

• DOI: 10.1523/jneurosci.2068-05.2005
• Publication Date: 2005-10-12T18:17:54Z
• Authors: Simona Occhi; Desirée Zambroni; Ubaldo Del Carro; Stefano Amadio; Erich E. Sirkowski; Steven S. Scherer; Kevin P. Campbell; Steven A. Moore; Zulin-L. Chen; Sidney Strickland; Antonio Di Muzio; Antonino Uncini; Lawrence Wrabetz; M. Laura Feltri
• Keywords: Dystroglycan; Schwann cell; Node of Ranvier

Nodes of Ranvier are specialized axonal domains, at which voltage-gated sodium channels cluster. How axons cluster molecules in discrete domains is mostly unknown. Both and glia probably provide constraining mechanisms that contribute to domain formation. Proper channel clustering peripheral nerves depends on contact from Schwann cell microvilli, where least one molecule, gliomedin, binds the complex induces its clustering. Furthermore, mice lacking dystroglycan have aberrant microvilli poorly clustered channels. Dystroglycan could interact basal lamina or axonglial surface. Because a laminin receptor, 2 mutations [merosin-deficient congenital muscular dystrophy (MDC1A)] cause reduced nerve conduction velocity, we asked whether laminins involved. Here, show composition both nodes differs internodes. Mice defective formed abnormal clusters. These abnormalities similar, albeit less severe, than those dystroglycan. However, all severe nodal abnormalities, suggesting other compensate for lack 2. Thus, although located distance axoglial junction, they required proper Laminins, through their specific receptors cytoskeletal linkages, may participate formation constrain clusters nodes. Finally, present patient with MDC1A, providing molecular basis velocity this disorder.