Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination

Soo Jin Chun, Matthew N. Rasband, Richard L. Sidman, Amyn A. Habib, Timothy Vartanian

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Early steps in myelination in the central nervous system (CNS) include a specialized and extreme form of cell spreading in which oligodendrocytes extend large lamellae that spiral around axons to form myelin. Recent studies have demonstrated that laminin-2 (LN-2; α2β1γ1) stimulates oligodendrocytes to extend elaborate membrane sheets in vitro (cell spreading), mediated by integrin α6β1. Although a congenital LN-2 deficiency in humans is associated with CNS white matter changes, LN-2-deficient (dy/ dy) mice have shown abnormalities primarily within the peripheral nervous system. Here, we demonstrate a critical role for LN-2 in CNS myelination by showing that dy/dy mice have quantitative and morphologic defects in CNS myelin. We have defined the molecular pathway through which LN-2 signals oligodendrocyte cell spreading by demonstrating requirements for phosphoinositide 3-kinase activity and integrin-linked kinase (ILK). Interaction of oligodendrocytes with LN-2 stimulates ILK activity. A dominant negative ILK inhibits LN-2-induced myelinlike membrane formation. A critical component of the myelination signaling cascade includes LN-2 and integrin signals through ILK.

Original languageEnglish (US)
Pages (from-to)397-408
Number of pages12
JournalJournal of Cell Biology
Volume163
Issue number2
DOIs
StatePublished - Oct 27 2003

Fingerprint

Oligodendroglia
Laminin
Central Nervous System
Myelin Sheath
Integrins
1-Phosphatidylinositol 4-Kinase
Membranes
Peripheral Nervous System
Axons
integrin-linked kinase

Keywords

  • Dy/dy mice
  • Focal adhesion
  • ILK
  • LN-2
  • PI3K

ASJC Scopus subject areas

  • Cell Biology

Cite this

Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. / Chun, Soo Jin; Rasband, Matthew N.; Sidman, Richard L.; Habib, Amyn A.; Vartanian, Timothy.

In: Journal of Cell Biology, Vol. 163, No. 2, 27.10.2003, p. 397-408.

Research output: Contribution to journalArticle

Chun, Soo Jin ; Rasband, Matthew N. ; Sidman, Richard L. ; Habib, Amyn A. ; Vartanian, Timothy. / Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. In: Journal of Cell Biology. 2003 ; Vol. 163, No. 2. pp. 397-408.
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