Tenascin C and tenascin R similarly prevent the formation of myelin membranes in a RhoA-dependent manner, but antagonistically regulate the expression of myelin basic protein via a separate pathway

Czopka, Tim, Von Holst, Alexander, Schmidt, Gudula, Ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 and Faissner, Andreas (2009) Tenascin C and tenascin R similarly prevent the formation of myelin membranes in a RhoA-dependent manner, but antagonistically regulate the expression of myelin basic protein via a separate pathway. Glia, 57 (16). pp. 1790-1801. ISSN 0894-1491

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Abstract

Membrane formation and the initiation of myelin gene expression are hallmarks of the differentiation of oligodendrocytes from their precursors. Here, we compared the roles of the two related extracellular matrix (ECM) glycoproteins Tenascin C (Tnc) and Tenascin R (Tnr) in oligodendrocyte differentiation. Oligodendrocyte precursors from Tnr-deficient mice exhibited reduced differentiation, as revealed by retarded expression of myelin basic protein (MBP) in culture. This could be rescued with purified Tnr. In contrast, when we cultured oligodendrocytes on a Tnc-containing, astrocyte-derived ECM, they barely expressed MBP. This inhibition could be overcome when we used ECM from astrocytes deficient for Tnc, suggesting that Tnc inhibits differentiation. In contrast to their antagonistic effect on differentiation, both Tnc and Tnr similarly inhibited morphologic maturation. When oligodendrocytes were cultured on the purified glycoproteins, process elaboration and membrane expansion were reduced. Both Tnc and Tnr interfered with the activation of the small GTPase RhoA. Conversely, RhoA and Rac1 activation induced by cytotoxic necrotizing factor 1 (CNF1) increased the formation of myelin membranes, whereas Y27632-mediated inhibition of the Rho-cascade prevented it without, however, affecting the fraction of MBP-expressing cells. Because Tnc and Tnr play antagonistic roles for differentiation and comparably inhibit morphologic maturation, we conclude that independent molecular pathways regulate these processes.

Item Type: Article
Uncontrolled Keywords: extracellular matrix,glycoprotein,oligodendrocyte,rho-gtpases,neurology,cellular and molecular neuroscience ,/dk/atira/pure/subjectarea/asjc/2800/2808
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 11:30
Last Modified: 13 Aug 2022 02:21
URI: https://ueaeprints.uea.ac.uk/id/eprint/86299
DOI: 10.1002/glia.20891

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