Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system.
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.
Pereira
Jorge A
JA
Institute of Cell Biology, Department of Biology, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland.
Benninger
Yves
Y
Baumann
Reto
R
Gonçalves
Ana Filipa
AF
Ozçelik
Murat
M
Thurnherr
Tina
T
Tricaud
Nicolas
N
Meijer
Dies
D
Fässler
Reinhard
R
Suter
Ueli
U
Relvas
João B
JB
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D019426:Integrases; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009186:Myelin Sheath / Q000502:physiology*; D017933:Peripheral Nervous System / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism; D000099200:Scaffold Protein ILK
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019426:Integrases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; D000099200:Scaffold Protein ILK; C045073:Cre recombinase; C049347:fasudil