Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains

Baron, Wia, Decker, Laurence, Colognato, Holly and Ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2003) Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains. Current Biology, 13 (2). pp. 151-155. ISSN 0960-9822

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Abstract

Individual growth factors can regulate multiple aspects of behavior within a single cell during differentiation, with each signaling pathway controlled independently and also responsive to other receptors such as cell surface integrins. The mechanisms by which this is achieved remain poorly understood. Here we use myelin-forming oligodendrocytes and their precursors to examine the role of lipid rafts, cholesterol and sphingolipid-rich microdomains of the cell membrane implicated in cell signaling [1]. In these cells, the growth factor PDGF has sequential and independent roles in proliferation and survival [2, 3]. We show that the oligodendrocyte PDGFα receptor becomes sequestered in a raft compartment at the developmental stage when PDGF ceases to promote proliferation, but is now required for survival. We also show that laminin-2, which is expressed on axons in the CNS and which provides a target-dependent signal for oligodendrocyte survival by amplification of PDGFαR signaling [4], induces clustering of the laminin binding integrin α6α1 with the PDGFαR-containing lipid raft domains. This extracellular matrix-induced colocalization of integrin and growth factor receptor generates a signaling environment within the raft for survival-promoting PI3K/Akt activity. These results demonstrate novel signaling roles for lipid rafts that ensure the separation and amplification of growth factor signaling pathways during development.

Item Type: Article
Additional Information: Funding Information: This work was supported by a Wellcome Trust Showcase award, a fellowship from the Dutch foundation for the support of MS research (W.B.), by a Marie Curie postdoctoral fellowship (L.D.), by fellowship F32-NS11035 from the National Institutes of Health (H.C.), and by a Wellcome Trust Research leave Fellowship (C.ff-C.). We are very grateful to Drs. Vito Quaranta and Carl Heldin for kind gifts of antisera and to Dr. Jackie Trotter and her colleagues Drs. Corinna Klein and Evi Kramer for help and advice with the lipid raft preparations.
Uncontrolled Keywords: neuroscience(all),biochemistry, genetics and molecular biology(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: 16 Jul 2022 12:30
Last Modified: 17 Jul 2022 00:29
URI: https://ueaeprints.uea.ac.uk/id/eprint/86348
DOI: 10.1016/S0960-9822(02)01437-9

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