αv-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation.
J Cell Biol
; 219(12)2020 12 07.
Article
en En
| MEDLINE
| ID: mdl-33141174
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 α5ß1 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 α5ß1 and αv-class integrins solely recognize the FN-RGD motif and that αv-class, but not α5ß1, 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Mutación
Límite:
Animals
Idioma:
En
Revista:
J Cell Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
España