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

ABSTRACT: 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 dictated by YAP/TAZ-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 fueling nutrient mTORC1 signaling. By orchestrating the transcription of a repertoire of cell-surface transporters, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 pathway activation. Dissociating mTORC1 from these nutrient inputs – elicited by the loss of Rag GTPases – inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. These findings define a pivotal role for YAP/TAZ-TEAD in steering endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Cell Of Umbilical Vein, Huvec Cell

SUBMITTER: Scientific Service Group Biomolecular Mass Spectrometry

LAB HEAD: Michael Potente

PROVIDER: PXD026872 | Pride | 2022-05-08

REPOSITORIES: Pride

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			Action	DRS
	20150707_SH_YuTing_YapTazIP_Huvec_GFP_Ctrl1_01.raw	Raw
	20150707_SH_YuTing_YapTazIP_Huvec_GFP_Ctrl1_02.raw	Raw
	20150707_SH_YuTing_YapTazIP_Huvec_GFP_Ctrl1_03.raw	Raw
	20150707_SH_YuTing_YapTazIP_Huvec_GFP_Ctrl1_04.raw	Raw
	20150707_SH_YuTing_YapTazIP_Huvec_GFP_Ctrl1_05.raw	Raw

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

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