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

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

dc.contributor.author	Benito Jardón, María
dc.contributor.author	Strohmeyer, Nico
dc.contributor.author	Ortega-Sanchís, Sheila
dc.contributor.author	Bharadwaj, Mitasha
dc.contributor.author	Moser, Markus
dc.contributor.author	Müller, Daniel J.
dc.contributor.author	Fässler, Reinhard
dc.contributor.author	Costell Rosselló, Mercedes
dc.date.accessioned	2020-11-24T15:01:54Z
dc.date.available	2020-11-24T15:01:54Z
dc.date.issued	2020
dc.identifier.uri	https://hdl.handle.net/10550/76461
dc.description.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 α5β1 and αv-class integrins. However, whether RGD is the sole binding site for αv-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 αv-class integrin binding and fibrillogenesis. To address this conflict, we employed single-cell force spectroscopy, engineered cells, and RGD motif-deficient mice (Fn1ΔRGD/ΔRGD) to search for additional αv-class integrin-binding sites. Our results demonstrate that α5β1 and αv-class integrins solely recognize the FN-RGD motif and that αv-class, but not α5β1, integrins retain FN-RGE binding. Furthermore, Fn1ΔRGD/ΔRGD tissues and cells assemble abnormal and dysfunctional FNΔRGD fibrils in a syndecan-dependent manner. Our data highlight the central role of FN-RGD and the functionality of FN-RGE for αv-class integrins.
dc.language.iso	eng
dc.relation.ispartof	Journal of Cell Biology, 2020, vol. 219, num. 12, p. 1-17
dc.rights.uri	info:eu-repo/semantics/openAccess
dc.source	Benito Jardón, María Strohmeyer, Nico Ortega-Sanchís, Sheila Bharadwaj, Mitasha Moser, Markus Müller, Daniel J. Fässler, Reinhard Costell Rosselló, Mercedes 2020 αv-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation Journal of Cell Biology 219 12 1 17
dc.subject	Biologia
dc.subject	Bioquímica
dc.title	αv-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation
dc.type	info:eu-repo/semantics/article
dc.date.updated	2020-11-24T15:01:55Z
dc.identifier.doi	https://doi.org/10.1083/jcb.202004198
dc.identifier.idgrec	141334