Lipid Rafts and Integrin Activation Regulate Oligodendrocyte Survival

Laurence Decker, Charles Ffrench-Constant

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3816-3825
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number15
DOIs
Publication statusPublished - 14 Apr 2004

Keywords

  • Apoptosis
  • Integrin activation
  • Lipid raft
  • MAPK
  • Oligodendrocyte
  • PDGF receptor
  • PI3K

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