The formation of paranodal spirals at the ends of CNS myelin sheaths requires the planar polarity protein Vangl2

Jarjour, Andrew A., Velichkova, Atanaska N., Boyd, Amanda, Lord, Kathryn M., Torsney, Carole, Henderson, Deborah J. and ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2020) The formation of paranodal spirals at the ends of CNS myelin sheaths requires the planar polarity protein Vangl2. Glia, 68 (9). pp. 1840-1858. ISSN 0894-1491

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Abstract

During axonal ensheathment, noncompact myelin channels formed at lateral edges of the myelinating process become arranged into tight paranodal spirals that resemble loops when cut in cross section. These adhere to the axon, concentrating voltage-dependent sodium channels at nodes of Ranvier and patterning the surrounding axon into distinct molecular domains. The signals responsible for forming and maintaining the complex structure of paranodal myelin are poorly understood. Here, we test the hypothesis that the planar cell polarity determinant Vangl2 organizes paranodal myelin. We show that Vangl2 is concentrated at paranodes and that, following conditional knockout of Vangl2 in oligodendrocytes, the paranodal spiral loosens, accompanied by disruption to the microtubule cytoskeleton and mislocalization of autotypic adhesion molecules between loops within the spiral. Adhesion of the spiral to the axon is unaffected. This results in disruptions to axonal patterning at nodes of Ranvier, paranodal axon diameter and conduction velocity. When taken together with our previous work showing that loss of the apico-basal polarity protein Scribble has the opposite phenotype—loss of axonal adhesion but no effect on loop–loop autotypic adhesion—our results identify a novel mechanism by which polarity proteins control the shape of nodes of Ranvier and regulate conduction in the CNS.

Item Type:	Article
Additional Information:	Funding Information: We thank David Lyons and Anna Williams for their helpful comments about the manuscript, and Bertrand Vernay for his assistance with image analysis. All authors reviewed and commented on the article before submission. Funding for this project was provided by the Wellcome Trust and the UK Multiple Sclerosis Society.
Uncontrolled Keywords:	cell polarity,myelin,node of ranvier,oligodendrocyte,paranode,vangl2,neurology,cellular and molecular neuroscience ,/dk/atira/pure/subjectarea/asjc/2800/2808
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	18 Jul 2022 16:30
Last Modified:	23 Oct 2022 03:55
URI:	https://ueaeprints.uea.ac.uk/id/eprint/86488
DOI:	10.1002/glia.23809

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