2026-07-21T14:14:56Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/188702024-11-30T01:24:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Ong, Yu Ting
author
Andrade, Jorge
author
Armbruster, Max
author
Shi, Chenyue
author
Castro, Marco
author
Costa, Ana S H
author
Sugino, Toshiya
author
Eelen, Guy
author
Zimmermann, Barbara
author
Wilhelm, Kerstin
author
Lim, Joseph
author
Watanabe, Shuichi
author
Guenther, Stefan
author
Schneider, Andre
author
Zanconato, Francesca
author
Kaulich, Manuel
author
Pan, Duojia
author
Braun, Thomas
author
Gerhardt, Holger
author
Efeyan, Alejo
author
Carmeliet, Peter
author
Piccolo, Stefano
author
Grosso, Ana Rita
author
Potente, Michael
funder
Max Planck Society
2024-03-01T11:12:39Z
2024-03-01T11:12:39Z
2022-06
Nat Metab . 2022;4(6):672-682.
10.1038/s42255-022-00584-y
2522-5812
Nature metabolism
35726026
http://hdl.handle.net/20.500.12105/18870
Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are instructed by Yes-associated protein 1 (YAP)/WW domain-containing transcription regulator 1 (WWTR1/TAZ)-transcriptional enhanced associate domain (TEAD): a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2 and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fuelling nutrient-dependent mTORC1 signalling. By orchestrating the transcription of a repertoire of cell-surface transporters, including the large neutral amino acid transporter SLC7A5, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 activation. Dissociating mTORC1 from these nutrient inputs-elicited by the loss of Rag GTPases-inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. Together, these findings define a pivotal role for YAP/TAZ-TEAD in controlling endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.
eng
A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth.
journal article
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