Assembly of CNS Nodes of Ranvier in Myelinated Nerves Is Promoted by the Axon Cytoskeleton.
Nodes of Ranvier in the axons of myelinated neurons are exemplars of the specialized cell surface domains typical of polarized cells. They are rich in voltage-gated sodium channels (Nav) and thus underpin rapid nerve impulse conduction in the vertebrate nervous system [1]. Although nodal proteins cluster in response to myelination, how myelin-forming glia influence nodal assembly is poorly understood. An axoglial adhesion complex comprising glial Neurofascin155 and axonal Caspr/Contactin flanks mature nodes [2]. We have shown that assembly of this adhesion complex at the extremities of migrating oligodendroglial processes promotes process convergence along the axon during central nervous system (CNS) node assembly [3]. Here we show that anchorage of this axoglial complex to the axon cytoskeleton is essential for efficient CNS node formation. When anchorage is disrupted, both the adaptor Protein 4.1B and the cytoskeleton protein βII spectrin are mislocalized in the axon, and assembly of the node of Ranvier is significantly delayed. Nodal proteins and migrating oligodendroglial processes are no longer juxtaposed, and single detached nodal complexes replace the symmetrical heminodes found in both the CNS and peripheral nervous system (PNS) during development. We propose that axoglial adhesion complexes contribute to the formation of an interface between cytoskeletal elements enriched in Protein 4.1B and βII spectrin and those enriched in nodal ankyrinG and βIV spectrin. This clusters nascent nodal complexes at heminodes and promotes their timely coalescence to form the mature node of Ranvier. These data demonstrate a role for the axon cytoskeleton in the assembly of a critical neuronal domain, the node of Ranvier.
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK.
Veronica
V
Brivio
Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille-UMR 7286, CNRS, 13344 Marseille, France.
Catherine
C
Faivre-Sarrailh
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Elior
E
Peles
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK.
Diane L
DL
Sherman
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK. Electronic address: peter.brophy@ed.ac.uk.
Peter J
PJ
Brophy
D000818:Animals; D001369:Axons / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000254:growth & development*; D003599:Cytoskeleton / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism*; D013049:Spectrin
D002352:Carrier Proteins; D008840:Microfilament Proteins; D013049:Spectrin; C488402:Epb41l3 protein, mouse
CNS; myelination; node of Ranvier; paranodal axoglial junction