PUBLICATION
Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance
- Authors
- 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.
- ID
- ZDB-PUB-170330-7
- 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
-
- Blood Vessels/metabolism*
- Protein Serine-Threonine Kinases/metabolism
- Cell Nucleus/metabolism
- Perfusion
- Humans
- Adaptor Proteins, Signal Transducing/metabolism*
- Endothelial Cells/metabolism*
- Shear Strength
- Transcriptional Activation/genetics
- Trans-Activators/metabolism*
- Signal Transduction/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- Phosphoproteins/metabolism*
- Stress, Mechanical
- Zebrafish Proteins/metabolism*
- Human Umbilical Vein Endothelial Cells/metabolism
- Hemorheology*
- Transcription, Genetic
- Protein Transport
- Actins/metabolism
- Animals
- PubMed
- 28350986 Full text @ Dev. Cell
Citation
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. (2017) Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance. Developmental Cell. 40:523-536.e6.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping