Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons
- University of Edinburgh, United Kingdom
- University of Nottingham, United Kingdom
- University of Strathclyde, United Kingdom
Abstract
Voltage-gated sodium channels cluster in macromolecular complexes at nodes of Ranvier to promote rapid nerve impulse conduction in vertebrate nerves. Node assembly in peripheral nerves is thought to be initiated at heminodes at the extremities of myelinating Schwann cells and fusion of heminodes results in the establishment of nodes. Here we show that assembly of 'early clusters' of nodal proteins in the murine axonal membrane precedes heminode formation. The Neurofascin (Nfasc) proteins are essential for node assembly, and the formation of early clusters also requires neuronal Nfasc. Early clusters are mobile and their proteins are dynamically recruited by lateral diffusion. They can undergo fusion not only with each other but also with heminodes thus contributing to the development of nodes in peripheral axons. The formation of early clusters constitutes the earliest stage in peripheral node assembly and expands the repertoire of strategies that have evolved to establish these essential structures.
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Funding
Wellcome Trust (107008)
- Peter J Brophy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work conformed to UK legislation (Scientific Procedures) Act 1986 and to the University of Edinburgh Ethical Review policy and was performed under Project Licence No. P0F4A25E9 from the Animals in Science Regulation Unit of the UK Home Office.
Copyright
© 2021, Malavasi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons
eLife 10:e68089.
https://doi.org/10.7554/eLife.68089
