β3 integrin–mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent manner

Laure Fourel (1) , Anne Valat (1) , Eva Faurobert (2) , Raphaël Guillot (1) , Ingrid Bourrin-Reynard , Kefeng Ren (1) , Laurence Lafanechère (3) , Emmanuelle Planus (3) , Catherine Picart (1) , Corinne Albiges-Rizo (3)

1 LMGP - Laboratoire des matériaux et du génie physique
2 DySAD - Dynamique des systèmes d'adhérence et différenciation
3 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble

Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin–dependent C2C12 cell spreading by overriding the soft signal of the biomaterial and impacting actin organization and adhesion site dynamics. In turn, αvβ3 integrin is required to mediate BMP-2–induced Smad signaling through a Cdc42–Src–FAK–ILK pathway. β3 integrin regulates a multistep process to control first BMP-2 receptor activity and second the inhibitory role of GSK3 on Smad signaling. Overall, our results show that BMP receptors and β3 integrin work together to control Smad signaling and tensional homeostasis, thereby coupling cell adhesion and fate commitment, two fundamental aspects of developmental biology and regenerative medicine.%U http://jcb.rupress.org/content/jcb/212/6/693.full.pdf

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire; Interactions cellulaires [q-bio.CB]

Laure Fourel, Anne Valat, Eva Faurobert, Raphaël Guillot, Ingrid Bourrin-Reynard, et al.. β3 integrin–mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent manner. Journal of Cell Biology, 2016, 212 (6), pp.693-706. ⟨10.1083/jcb.201508018⟩. ⟨hal-02324366⟩