Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance

Nakajima, Hiroyuki and Yamamoto, Kimiko and Agarwala, Sobhika and Terai, Kenta and Fukui, Hajime and Fukuhara, Shigetomo and Ando, Koji and Miyazaki, Takahiro and Yokota, Yasuhiro and Schmelzer, Etienne and Belting, Heinz-Georg and Affolter, Markus and Lecaudey, Virginie and Mochizuki, Naoki. (2017) Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance. Developmental Cell, 40 (6). pp. 523-536.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)
UniBasel Contributors:Affolter, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Oct 2017 09:44
Deposited On:20 Oct 2017 09:44

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