Lipid Rafts and Integrin Activation Regulate Oligodendrocyte Survival

Decker, Laurence and Ffrench-Constant, Charles ORCID: (2004) Lipid Rafts and Integrin Activation Regulate Oligodendrocyte Survival. Journal of Neuroscience, 24 (15). pp. 3816-3825. ISSN 0270-6474

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Newly formed oligodendrocytes in the CNS derive survival cues from their target axons. These cues are provided in part by laminins expressed on the axon, which are recognized by α6β1 integrin on the oligdendrocyte and amplify platelet-derived growth factor (PDGF) signaling through the phosphatidylinositol 3′-kinase (PI3K) pathway. The α6β1 integrin is localized in oligodendrocyte lipid rafts. We show here using the sphingolipid synthesis inhibitor fumonisin-B1 to deplete rafts that this localization is important for normal survival signaling, because depletion increases oligodendrocyte apoptosis and inhibits PI3K signaling. We have shown previously that PDGF-mediated integrin activation is an important component of oligodendrocyte proliferation signaling, and here we present evidence that a similar mechanism operates in survival signaling. Integrin activation using manganese increases raft localization and rescues the effects of both raft depletion and PDGF removal on survival and PI3K signaling. Together, these results point to an essential role for rafts in oligodendrocyte survival signaling on the basis of the provision of a favorable environment for growth factor-mediated integrin activation.

Item Type: Article
Uncontrolled Keywords: apoptosis,integrin activation,lipid raft,mapk,oligodendrocyte,pdgf receptor,pi3k,neuroscience(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: 22 Oct 2022 18:38
DOI: 10.1523/JNEUROSCI.5725-03.2004

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