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YAP/TAZ as new regulatory hub of VEGF signaling [ChIP]

ABSTRACT: VEGF is a major driver of blood vessel formation. However, the signal transduction pathways culminating into the biological consequences of VEGF signaling are partially understood. Here we show that the Hippo pathway effectors YAP and TAZ, work as a regulatory hub in mediating VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton remodeling, and that activated YAP/TAZ induce a transcriptional program that results in the expression of a set of genes to further control cytoskeleton dynamics, and thus ensure a proper angiogenic response. YAP/TAZ deletion also results in VEGFR2 trafficking defects from the Golgi to the plasma membrane. Together, our study establishes YAP/TAZ as a central regulatory hub that mediates VEGF signaling, and hence, regulates angiogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94856 | GEO | 2019/03/12

REPOSITORIES: GEO

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YAP/TAZ as new regulatory hub of VEGF signaling [RNA]

Project description:VEGF is a major driver of blood vessel formation. However, the signal transduction pathways culminating into the biological consequences of VEGF signaling are partially understood. Here we show that the Hippo pathway effectors YAP and TAZ, work as a regulatory hub in mediating VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton remodeling, and that activated YAP/TAZ induce a transcriptional program that results in the expression of a set of genes to further control cytoskeleton dynamics, and thus ensure a proper angiogenic response. YAP/TAZ deletion also results in VEGFR2 trafficking defects from the Golgi to the plasma membrane. Together, our study establishes YAP/TAZ as a central regulatory hub that mediates VEGF signaling, and hence, regulates angiogenesis.

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YAP/TAZ as new regulatory hub of VEGF signaling

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BMP/Taz-Hippo signaling modulates VEGF-mediated angiogenesis

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Project description:YAP/TAZ as new regulatory hub of VEGF signaling [RNA]

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Project description: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.

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