The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System

Jarjour, Andrew A., Boyd, Amanda, Dow, Lukas E., Holloway, Rebecca K., Goebbels, Sandra, Humbert, Patrick O., Williams, Anna and ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2015) The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System. PLoS Biology, 13 (3). ISSN 1544-9173

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Abstract

The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination.

Item Type: Article
Uncontrolled Keywords: neuroscience(all),biochemistry, genetics and molecular biology(all),immunology and microbiology(all),agricultural and biological sciences(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 22:30
Last Modified: 12 Aug 2022 05:38
URI: https://ueaeprints.uea.ac.uk/id/eprint/86257
DOI: 10.1371/journal.pbio.1002107

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