Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system

Jorge A Pereira, Yves Benninger, Reto Baumann, Ana Filipa Gonçalves, Murat Ozçelik, Tina Thurnherr, Nicolas Tricaud, Dies Meijer, Reinhard Fässler, Ueli Suter, João B Relvas

Research output: Contribution to journalArticlepeer-review

Abstract

During development, Schwann cells (SCs) interpret different extracellular cues to regulate their migration, proliferation, and the remarkable morphological changes associated with the sorting, ensheathment, and myelination of axons. Although interactions between extracellular matrix proteins and integrins are critical to some of these processes, the downstream signaling pathways they control are still poorly understood. Integrin-linked kinase (ILK) is a focal adhesion protein that associates with multiple binding partners to link integrins to the actin cytoskeleton and is thought to participate in integrin and growth factor-mediated signaling. Using SC-specific gene ablation, we report essential functions for ILK in radial sorting of axon bundles and in remyelination in the peripheral nervous system. Our in vivo and in vitro experiments show that ILK negatively regulates Rho/Rho kinase signaling to promote SC process extension and to initiate radial sorting. ILK also facilitates axon remyelination, likely by promoting the activation of downstream molecules such as AKT/protein kinase B.
Original languageEnglish
Pages (from-to)147-61
Number of pages15
JournalJournal of Cell Biology
Volume185
Issue number1
DOIs
Publication statusPublished - 6 Apr 2009

Keywords

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Animals
  • Axons
  • Cells, Cultured
  • Integrases
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Myelin Sheath
  • Peripheral Nervous System
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Regeneration
  • Schwann Cells
  • Signal Transduction
  • rho-Associated Kinases

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