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

被引:78
作者
Colognato, Holly [1 ]
Galvin, Jason
Wang, Zhen
Relucio, Jenne
Nguyen, Tom
Harrison, David
Yurchenco, Peter D.
Ffrench-Constant, Charles
机构
[1] SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY 11794 USA
[2] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[3] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 1QP, England
[4] Univ Med & Dent New Jersey, Dept Pathol, Piscataway, NJ 08854 USA
来源
DEVELOPMENT | 2007年 / 134卷 / 09期
基金
英国医学研究理事会; 英国惠康基金;
关键词
dystroglycan; oligodendrocyte; laminin; myelin; integrin; DRG; rat;
D O I
10.1242/dev.02819
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-1integrins 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.
引用
收藏
页码:1723 / 1736
页数:14
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