YAP/TAZ-CDC42 signaling regulates vascular tip cell migration.
basic_science · Level V
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- Record sourced from PubMed, PMID 28973878.
- Also identified by DOI 10.1073/pnas.1704030114 and PMC identifier 5642684.
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Abstract
Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by <i>Lats1</i>/<i>2</i>-deletion blocked endothelial migration and phenocopied <i>Yap/Taz</i>-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Cell Movement
- Endothelium, Vascular
- Neovascularization, Physiologic
- Phosphoproteins
- Transcription Factors
- cdc42 GTP-Binding Protein