Endothelial Yap1 functions as a mechanotransducer to maintain blood vessels

抄録

Endothelial cells lining vascular lumen face to blood flow and respond to the mechanical stress from blood flow. Endothelial cells sprouts from pre-existing blood vessels by angiogenesis and become stabilized by flow from the pre-existing vessels. This stabilization is maintained by shear flow. Therefore, we investigated how shear flow stabilizes the endothelial cells.

　We found that Yap1-dependent transcription in endothelial cells is activated by flow in living zebrafish embryos and green fluorescent protein-tagged YAP enters into the nucleus of endothelial cells. In cultured mammalian endothelial cells, shear induces the cortical actin assembly at the inter-endothelial junctions. YAP (corresponding to zebrafish Yap1) binding to angiomotin is released from the angiomotion (Amot)-YAP complex, because Amot binds to the assembled cortical actin fibers at the cell-cell junctions upon shear stress. We further examined the effect of depletion of Amot family members (Amots: Amot and Amot-like proteins) on the localization of YAP and found that YAP is localized in the nucleus in the endothelial cells depleted of Amots. Yap1 mutant zebrafish exhibited defects in vascular stability in the dorsal longitudinal anastomotic vesels. Collectively our data indicate that endothelial Yap1 functions in response to flow to maintain blood vessels.