Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. Academic Article uri icon

Overview

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; alpha2beta1gamma1) stimulates oligodendrocytes to extend elaborate membrane sheets in vitro (cell spreading), mediated by integrin alpha6beta1. 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.

publication date

  • October 27, 2003

Research

keywords

  • Central Nervous System
  • Laminin
  • Myelin Sheath
  • Oligodendroglia
  • Protein Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC2173507

Scopus Document Identifier

  • 0242266910

PubMed ID

  • 14581460

Additional Document Info

volume

  • 163

issue

  • 2