6533b7d4fe1ef96bd12629b7

RESEARCH PRODUCT

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

Irene Gimeno-lluchMaría Benito-jardónTobias PetzoldGabriele ZuchtriegelChristoph A. ReichelSarah KlapprothMitasha BharadwajMercedes CostellDaniel J. Müller

subject

0301 basic medicineMouseQH301-705.5extracellular matrixScienceExtracellular matrix componentIntegrinHemorrhageGeneral Biochemistry Genetics and Molecular BiologyExtracellular matrixMice03 medical and health sciencesfibronectinAnimalsBiology (General)Cell adhesionRGD motifMice KnockoutGeneral Immunology and MicrobiologybiologyCell adhesion moleculeChemistryGeneral NeuroscienceQRThrombosiscell adhesionCell BiologyGeneral MedicineFibronectinsCell biologyFibronectinCrosstalk (biology)030104 developmental biologymechanosignalingImmunologyintegrinsbiology.proteinMedicineResearch Article

description

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.

yearjournalcountryeditionlanguage
2017-01-16eLife
https://doi.org/10.7554/elife.22264