YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis

Autor:	Georg Halder, Xiaohong Wang, Severino Urban, Tamás Fischer, Rakesh K. Jain, Carmen Ruiz de Almodovar, Laura Castro, Lars Riedemann, Frank Winkler, Aida Freire Valls, Massimilano Mazzone, Ying Shen, Iván M. Moya, Gergely Solecki, Géza Schermann, Thomas Schmidt
Rok vydání:	2017
Předmět:	TAZ Vascular Endothelial Growth Factor A 0301 basic medicine Transcription Genetic Angiogenesis Golgi Apparatus Cell Cycle Proteins angiogenesis Gene Knockout Techniques Mice chemistry.chemical_compound CNS vascularization Models Cell Movement Cytoskeleton Tumor Neovascularization Pathologic Adaptor Proteins Brain VEGF Cell biology Vascular endothelial growth factor Actin Cytoskeleton Vascular endothelial growth factor A VEGFR2 YAP Signal transduction Transcription Signal Transduction Chromatin Immunoprecipitation hippo pathway Embryonic Development Neovascularization Physiologic Biology Models Biological General Biochemistry Genetics and Molecular Biology Cell Line endothelial cells YAP/TAZ Adaptor Proteins Signal Transducing Animals Animals Newborn Cell Line Tumor Cell Membrane Cell Nucleus Endothelial Cells Gene Deletion Gene Silencing Phosphoproteins Trans-Activators Vascular Endothelial Growth Factor Receptor-2 YAP-Signaling Proteins 03 medical and health sciences Genetic Physiologic Molecular Biology Neovascularization Pathologic Hippo signaling pathway Signal Transducing Kinase insert domain receptor Cell Biology Newborn Biological Actin cytoskeleton 030104 developmental biology chemistry Developmental Biology
Zdroj:	Developmental Cell. 42:462-478.e7
ISSN:	1534-5807
Popis:	Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate 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 and that activated YAP/TAZ induce a transcriptional program to further control cytoskeleton dynamics and thus establish a feedforward loop that ensures a proper angiogenic response. Lack of YAP/TAZ also results in altered cellular distribution of VEGFR2 due to trafficking defects from the Golgi apparatus to the plasma membrane. Altogether, our study identifies YAP/TAZ as central mediators of VEGF signaling and therefore as important regulators of angiogenesis.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::23f32f4d51f34e13192f32a8c04c4758 https://doi.org/10.1016/j.devcel.2017.08.002 Zobrazit plný text záznamu