RRC ID 66025
著者 Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazaki T, Yokota Y, Schmelzer E, Belting HG, Affolter M, Lecaudey V, Mochizuki N.
タイトル Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance.
ジャーナル Dev Cell
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.
巻・号 40(6)
ページ 523-536.e6
公開日 2017-3-27
DOI 10.1016/j.devcel.2017.02.019
PII S1534-5807(17)30115-6
PMID 28350986
MeSH 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 Intercellular Signaling Peptides and Proteins Membrane Proteins Perfusion Phosphoproteins / metabolism* Protein Serine-Threonine Kinases / metabolism Protein Transport Serine-Threonine Kinase 3 Shear Strength Signal Transduction / genetics Stress, Mechanical Trans-Activators / metabolism* Transcription Factors Transcription, Genetic Transcriptional Activation / genetics YAP-Signaling Proteins Zebrafish / embryology Zebrafish / genetics Zebrafish Proteins / metabolism*
IF 10.092
リソース情報
ゼブラフィッシュ Tg(UAS:GFP)