The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling

Vascular endothelial (VE)-cadherin transfers intracellular signals contributing to vascular hemostasis. Signaling through VE-cadherin requires association and activity of different intracellular partners. Yes-associated protein (YAP)/TAZ transcriptional cofactors are important regulators of cell growth and organ size. We show that EPS8, a signaling adapter regulating actin dynamics, is a novel partner of VE-cadherin and is able to modulate YAP activity. By biochemical and imaging approaches, we demonstrate that EPS8 associates with the VE-cadherin complex of remodeling junctions promoting YAP translocation to the nucleus and transcriptional activation. Conversely, in stabilized junctions, 14-3-3-YAP associates with the VE-cadherin complex, whereas Eps8 is excluded. Junctional association of YAP inhibits nuclear translocation and inactivates its transcriptional activity both in vitro and in vivo in Eps8-null mice. The absence of Eps8 also increases vascular permeability in vivo, but did not induce other major vascular defects. Collectively, we identified novel components of the adherens junction complex, and we introduce a novel molecular mechanism through which the VE-cadherin complex controls YAP transcriptional activity.

Disanza, Andrea (författare)
Bravi, Luca (författare)
Barrios-Rodiles, Miriam (författare)
Corada, Monica (författare)
Frittoli, Emanuela (författare)
Savorani, Cecilia (författare)
Lampugnani, Maria Grazia (författare)
Boggetti, Barbara (författare)
Niessen, Carien (författare)
Wrana, Jeff L (författare)
Scita, Giorgio (författare)
Dejana, ElisabettaUppsala universitet,Vaskulärbiologi(Swepub:uu)elide443 (författare)
Uppsala universitetVaskulärbiologi (creator_code:org_t)

Ingår i:Journal of Cell Biology: Rockefeller University Press211:6, s. 1177-11920021-95251540-8140

Av författaren/redakt...: Giampietro, Cost ...; Disanza, Andrea; Bravi, Luca; Barrios-Rodiles, ...; Corada, Monica; Frittoli, Emanue ...; visa fler...; Savorani, Cecili ...; Lampugnani, Mari ...; Boggetti, Barbar ...; Niessen, Carien; Wrana, Jeff L; Scita, Giorgio; Dejana, Elisabet ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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