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Journal Article

alpha v-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation

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Moser,  Markus
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Fässler,  Reinhard
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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jcb_202004198.pdf
(Publisher version), 8MB

Supplementary Material (public)

jcb_202004198_tables1.docx
(Supplementary material), 20KB

Citation

Benito-Jardon, M., Strohmeyer, N., Ortega-Sanchis, S., Bharadwaj, M., Moser, M., Mueller, D. J., et al. (2020). alpha v-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation. The Journal of Cell Biology, 219(12): e202004198. doi:10.1083/jcb.202004198.


Cite as: http://hdl.handle.net/21.11116/0000-0008-0B2A-E
Abstract
Fibronectin (FN) is an essential glycoprotein of the extracellular matrix; binds integrins, syndecans, collagens, and growth factors; and is assembled by cells into complex fibrillar networks. The RGD motif in FN facilitates cell binding- and fibrillogenesis through binding to alpha 5 beta 1 and alpha v-class integrins. However, whether RGD is the sole binding site for alpha v-class integrins is unclear. Most notably, substituting aspartate with glutamate (RGE) was shown to eliminate integrin binding in vitro, while mouse genetics revealed that FNRGE preserves alpha v-class integrin binding and fibrillogenesis. To address this conflict, we employed single-cell force spectroscopy, engineered cells, and RGD motif-deficient mice (Fn1(Delta RGD/Delta RGD)) to search for additional alpha v-class integrin-binding sites. Our results demonstrate that alpha 5 beta 1 and alpha v-class integrins solely recognize the FN-RGD motif and that av-class, but not alpha 5 beta 1, integrins retain FN-RGE binding. Furthermore, Fn1(Delta RGD/Delta RGD) tissues and cells assemble abnormal and dysfunctional FNARGD fibrils in a syndecan-dependent manner. Our data highlight the central role of FN Delta RGD and the functionality of FN-RGE for alpha v-class integrins.