The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes

eLife

Mitasha Bharadwaj¹  Sarah Klapproth¹  Maria Benito-Jardón²  Tobias Petzold²  Gabriele Zuchtriegel³  Christoph A Reichel³  Daniel J Müller⁴  Mercedes Costell⁵  Irene Gimeno-LLuch⁵ 

[1] Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina, Universitat de València, Burjassot, Spain;Department of Biochemistry and Molecular Biology, Universitat de València, Burjassot, Spain;Eidgenössische Technische Hochschule Zürich, Basel, Switzerland;Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany;Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany;

关键词: integrins;    fibronectin;    mechanosignaling;    extracellular matrix;    cell adhesion;   

DOI  :  10.7554/eLife.22264

来源: DOAJ

【 摘 要 】

Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of α5β1 with the RGD, but essential to re-enforce the binding of α5β1/αIIbβ3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when αvβ3 integrin levels decrease below a critical level.

【 授权许可】

Unknown