Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier

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

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Pages (from-to)9418-9427
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number41
DOIs
Publication statusPublished - Oct 12 2005

Fingerprint

Dystroglycans
Ranvier's Nodes
Sodium Channels
Schwann Cells
Laminin
Cluster Analysis
Microvilli
Axons
Neural Conduction
Neuroglia
Laminin Receptors
Voltage-Gated Sodium Channels
Peripheral Nerves
Basement Membrane
Sodium

Keywords

  • Dystrophic
  • Laminin
  • Microvilli
  • Node of Ranvier
  • Schwann cell
  • Sodium channels

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier. / Occhi, Simona; Zambroni, Desirée; Del Carro, Ubaldo; Amadio, Stefano; Sirkowski, Erich E.; Scherer, Steven S.; Campbell, Kevin P.; Moore, Steven A.; Chen, Zulin L.; Strickland, Sidney; Di Muzio, Antonio; Uncini, Antonino; Wrabetz, Lawrence; Feltri, M. Laura.

In: Journal of Neuroscience, Vol. 25, No. 41, 12.10.2005, p. 9418-9427.

Research output: Contribution to journalArticle

Occhi, S, Zambroni, D, Del Carro, U, Amadio, S, Sirkowski, EE, Scherer, SS, Campbell, KP, Moore, SA, Chen, ZL, Strickland, S, Di Muzio, A, Uncini, A, Wrabetz, L & Feltri, ML 2005, 'Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier', Journal of Neuroscience, vol. 25, no. 41, pp. 9418-9427. https://doi.org/10.1523/JNEUROSCI.2068-05.2005
Occhi, Simona ; Zambroni, Desirée ; Del Carro, Ubaldo ; Amadio, Stefano ; Sirkowski, Erich E. ; Scherer, Steven S. ; Campbell, Kevin P. ; Moore, Steven A. ; Chen, Zulin L. ; Strickland, Sidney ; Di Muzio, Antonio ; Uncini, Antonino ; Wrabetz, Lawrence ; Feltri, M. Laura. / Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 41. pp. 9418-9427.
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AU - Amadio, Stefano

AU - Sirkowski, Erich E.

AU - Scherer, Steven S.

AU - Campbell, Kevin P.

AU - Moore, Steven A.

AU - Chen, Zulin L.

AU - Strickland, Sidney

AU - Di Muzio, Antonio

AU - Uncini, Antonino

AU - Wrabetz, Lawrence

AU - Feltri, M. Laura

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N2 - 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 axons and glia probably provide constraining mechanisms that contribute to domain formation. Proper sodium channel clustering in peripheral nerves depends on contact from Schwann cell microvilli, where at least one molecule, gliomedin, binds the sodium channel complex and induces its clustering. Furthermore, mice lacking Schwann cell dystroglycan have aberrant microvilli and poorly clustered sodium channels. Dystroglycan could interact at the basal lamina or at the axon-glial surface. Because dystroglycan is a laminin receptor, and laminin 2 mutations [merosin-deficient congenital muscular dystrophy (MDC1A)] cause reduced nerve conduction velocity, we asked whether laminins are involved. Here, we show that the composition of both laminins and the dystroglycan complex at nodes differs from that of internodes. Mice defective in laminin 2 have poorly formed microvilli and abnormal sodium clusters. These abnormalities are similar, albeit less severe, than those of mice lacking dystroglycan. However, mice lacking all Schwann cell laminins show severe nodal abnormalities, suggesting that other laminins compensate for the lack of laminin 2. Thus, although laminins are located at a distance from the axoglial junction, they are required for proper clustering of sodium channels. Laminins, through their specific nodal receptors and cytoskeletal linkages, may participate in the formation of mechanisms that constrain clusters at nodes. Finally, abnormal sodium channel clusters are present in a patient with MDC1A, providing a molecular basis for the reduced nerve conduction velocity in this disorder.

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