Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

Colognato, Holly, Galvin, Jason, Wang, Zhen, Relucio, Jenne, Nguyen, Tom, Harrison, David, Yurchenco, Peter D. and Ffrench-Constant, Charles ORCID: (2007) Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination. Development, 134 (9). pp. 1723-1736. ISSN 0950-1991

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Developmental abnormalities of myelination are observed in the brains of laminin-deficient humans and mice. The mechanisms by which these defects occur remain unknown. It has been proposed that, given their central role in mediating extracellular matrix (ECM) interactions, integrin receptors are likely to be involved. However, it is a non-integrin ECM receptor, dystroglycan, that provides the key linkage between the dystrophin-glycoprotein complex (DGC) and laminin in skeletal muscle basal lamina, such that disruption of this bridge results in muscular dystrophy. In addition, the loss of dystroglycan from Schwann cells causes myelin instability and disorganization of the nodes of Ranvier. To date, it is unknown whether dystroglycan plays a role during central nervous system (CNS) myelination. Here, we report that the myelinating glia of the CNS, oligodendrocytes, express and use dystroglycan receptors to regulate myelin formation. In the absence of normal dystroglycan expression, primary oligodendrocytes showed substantial deficits in their ability to differentiate and to produce normal levels of myelin-specific proteins. After blocking the function of dystroglycan receptors, oligodendrocytes failed both to produce complex myelin membrane sheets and to initiate myelinating segments when co-cultured with dorsal root ganglion neurons. By contrast, enhanced oligodendrocyte survival in, response to the ECM, in conjunction with growth factors, was dependent on interactions with beta-1 integrins and did not require dystroglycan. Together, these results indicate that laminins are likely to regulate CNS myelination by interacting with both integrin receptors and dystroglycan receptors, and that oligodendrocyte dystroglycan receptors may have a specific role in regulating terminal stages of myelination, such as myelin membrane production, growth, or stability.

Item Type: Article
Uncontrolled Keywords: drg,dystroglycan,integrin,laminin,myelin,oligodendrocyte,rat,molecular biology,developmental biology ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 11:31
Last Modified: 22 Oct 2022 18:37
DOI: 10.1242/dev.02819

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