Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance

Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Hiroyuki Nakajima, Kimiko Yamamoto, Sobhika Agarwala, Kenta Terai, Hajime Fukui, Shigetomo Fukuhara, Koji Ando, Takahiro Miyazaki, Yasuhiro Yokota, Etienne Schmelzer, Heinz-Georg Belting, Markus Affolter, Virginie Lecaudey, Naoki Mochizuki
Endothelial cells (ECs) line the inside of blood vessels and respond to mechanical cues generated by blood flow. Mechanical stimuli regulate the localization of YAP by reorganizing the actin cytoskeleton. Here we demonstrate blood-flow-mediated regulation of endothelial YAP in vivo. We indirectly monitored transcriptional activity of Yap1 (zebrafish YAP) and its spatiotemporal localization in living zebrafish and found that Yap1 entered the nucleus and promoted transcription in response to blood flow. In cultured human ECs, laminar shear stress induced nuclear import of YAP and its transcriptional activity in a manner independent of Hippo signaling. We uncovered a molecular mechanism by which flow induced the nuclear translocation of YAP through the regulation of filamentous actin and angiomotin. Yap1 mutant zebrafish showed a defect in vascular stability, indicating an essential role for Yap1 in blood vessels. Our data imply that endothelial Yap1 functions in response to flow to maintain blood vessels.

Graphical abstract

Teaser

Nakajima et al. monitor the spatiotemporal localization and transcriptional activity of Yap1 in ECs of living zebrafish and reveal that blood flow regulates localization of Yap1 through mechanotransduction signaling.


http://ift.tt/2nHJW9N