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  A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth

Ong, Y. T., Andrade, J., Armbruster, M., Shi, C., Castro, M., Costa, A. S. H., et al. (2022). A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth. NATURE METABOLISM, 4(6), 672-682. doi:10.1038/s42255-022-00584-y.

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Ong, Yu Ting1, Autor           
Andrade, Jorge1, Autor           
Armbruster, Max1, Autor           
Shi, Chenyue1, Autor           
Castro, Marco1, Autor           
Costa, Ana S. H., Autor
Sugino, Toshiya1, Autor           
Eelen, Guy, Autor
Zimmermann, Barbara1, Autor           
Wilhelm, Kerstin1, Autor           
Lim, Joseph1, Autor           
Watanabe, Shuichi2, Autor           
Guenther, Stefan2, Autor           
Schneider, Andre2, Autor           
Zanconato, Francesca, Autor
Kaulich, Manuel, Autor
Pan, Duojia, Autor
Braun, Thomas2, Autor           
Gerhardt, Holger, Autor
Efeyan, Alejo, Autor
Carmeliet, Peter, AutorPiccolo, Stefano, AutorGrosso, Ana Rita, AutorPotente, Michael1, Autor            mehr..
Affiliations:
1Angiogenesis & Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591701              
2Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 Zusammenfassung: Ong et al. report how YAP/TAZ and mTORC1 signalling intersect in endothelial cells to regulate nutrient acquisition and vascular growth.
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.

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 Datum: 2022-06-202022
 Publikationsstatus: Erschienen
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 Identifikatoren: ISI: 000813670700003
DOI: 10.1038/s42255-022-00584-y
PMID: 35726026
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Titel: NATURE METABOLISM
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 4 (6) Artikelnummer: - Start- / Endseite: 672 - 682 Identifikator: -