Glial and Neuronal Isoforms of Neurofascin Have Distinct Roles in the Assembly of Nodes of Ranvier in the Central Nervous System

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2008 Jun 25

PMID 18573915

Citations 95

Authors

Barbara Zonta

Steven Tait

Shona Melrose

Heather Anderson

Sheila Harroch

Jennifer Higginson

Diane L Sherman

Peter J Brophy

Affiliations

Soon will be listed here.

Abstract

Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes of Ranvier. Myelin-forming oligodendrocytes in the central nervous system (CNS) induce the clustering of sodium channels into nodal complexes flanked by paranodal axoglial junctions. However, the molecular mechanisms for nodal complex assembly in the CNS are unknown. Two isoforms of Neurofascin, neuronal Nfasc186 and glial Nfasc155, are components of the nodal and paranodal complexes, respectively. Neurofascin-null mice have disrupted nodal and paranodal complexes. We show that transgenic Nfasc186 can rescue the nodal complex when expressed in Nfasc(-/-) mice in the absence of the Nfasc155-Caspr-Contactin adhesion complex. Reconstitution of the axoglial adhesion complex by expressing transgenic Nfasc155 in oligodendrocytes also rescues the nodal complex independently of Nfasc186. Furthermore, the Nfasc155 adhesion complex has an additional function in promoting the migration of myelinating processes along CNS axons. We propose that glial and neuronal Neurofascins have distinct functions in the assembly of the CNS node of Ranvier.

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