ZFIN ID: ZDB-PUB-170330-7
Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance
Nakajima, H., Yamamoto, K., Agarwala, S., Terai, K., Fukui, H., Fukuhara, S., Ando, K., Miyazaki, T., Yokota, Y., Schmelzer, E., Belting, H.G., Affolter, M., Lecaudey, V., Mochizuki, N.
Date: 2017
Source: Developmental Cell   40: 523-536.e6 (Journal)
Registered Authors: Affolter, Markus, Belting, Heinz-Georg Paul (Henry), Fukuhara, Shigetomo, Fukui, Hajime, Lecaudey, Virginie, Mochizuki, Naoki, Nakajima, Hiroyuki, Terai, Kenta
Keywords: Hippo pathway, fluid shear stress, mechanotransduction, vascular remodeling
MeSH Terms:
  • Actins/metabolism
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Blood Vessels/metabolism*
  • Cell Nucleus/metabolism
  • Endothelial Cells/metabolism*
  • Hemorheology*
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Perfusion
  • Phosphoproteins/metabolism*
  • Protein Serine-Threonine Kinases/metabolism
  • Protein Transport
  • Shear Strength
  • Signal Transduction/genetics
  • Stress, Mechanical
  • Trans-Activators/metabolism*
  • Transcription, Genetic
  • Transcriptional Activation/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28350986 Full text @ Dev. Cell
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.