Expression of dominant-negative and chimeric subunits reveals an essential role for β1 integrin during myelination

Relvas, João B., Setzu, Anna, Baron, Wia, Buttery, Philip C., LaFlamme, Susan E., Franklin, Robin J.M. and Ffrench-Constant, Charles ORCID: (2001) Expression of dominant-negative and chimeric subunits reveals an essential role for β1 integrin during myelination. Current Biology, 11 (13). pp. 1039-1043. ISSN 0960-9822

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Myelination represents a remarkable example of cell specialization and cell-cell interaction in development. During this process, axons are wrapped by concentric layers of cell membrane derived either from central nervous system (CNS) oligodendrocytes or peripheral nervous system Schwann cells. In the CNS, oligodendrocytes elaborate a membranous extension with an area of more than 1000 times that of the cell body [1]. The mechanisms regulating this change in cell shape remain poorly understood. Signaling mechanisms regulated by cell surface adhesion receptors of the integrin family represent likely candidates. Integrins link the extracellular environment of the cell with both intracellular signaling molecules and the cytoskeleton and have been shown to regulate the activity of GTPases implicated in the control of cell shape [2]. Our previous work has established that oligodendrocytes and their precursors express a limited repertoire of integrins [3, 4]. One of these, the α6β1 laminin receptor, can interact with laminin-2 substrates to enhance oligodendrocyte myelin membrane formation in cell culture [5]. However, these experiments do not address the important question of integrin function during myelination in vivo, nor do they define the respective roles of the α and β subunits in the signaling pathways involved. Here, we use a dominant-negative approach to provide, for the first time, evidence that β1 integrin function is required for myelination in vivo and use chimeric integrins to dissect apart the roles of the extracellular and cytoplasmic domains of the α6 subunit in the signaling pathways of myelination.

Item Type: Article
Additional Information: Funding Information: This work was supported by the Medical Research Council and the Multiple Sclerosis Society of Great Britain and Northern Ireland. J.B.R. holds a fellowship (BPD 11785) from the Programa Praxis XXI of the FCT, Portugal, and C.f-C. holds a Research Leave Fellowship for Clinical Academics from the Wellcome Trust.
Uncontrolled Keywords: biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 13:30
Last Modified: 22 Oct 2022 18:38
DOI: 10.1016/S0960-9822(01)00292-5

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