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.

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Keywords Rho kinase, Schwann cell, animal cell, article, cell maturation, cell migration, cell proliferation, controlled study, cytoskeleton, in vivo study, mouse, nerve fiber, nonhuman, peripheral nervous system, priority journal, remyelinization
Persistent URL dx.doi.org/10.1083/jcb.200809008, hdl.handle.net/1765/16422
Citation
Pereira, J., Benninger, Y., Baumann, R., Goncalves, A.F., Özcelik, M., Thurnherr, T., … Relvas, J.B.. (2009). Integrin-linked kinase is required for radial sorting of axons and schwann cell remyelination in the peripheral nervous system. The Journal of Cell Biology, 185(1), 147–161. doi:10.1083/jcb.200809008