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Published on: October 7, 2011
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YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis.
Xiaohong Wang1, Aida Freire Valls2, Géza Schermann1
1Biochemistry Center (BZH), University of Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Developmental Cell
|September 5, 2017
Summary
Vascular endothelial growth factor (VEGF) activates YAP and TAZ, crucial for blood vessel formation. These proteins regulate cytoskeleton dynamics and VEGFR2 trafficking, ensuring proper angiogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, the process of new blood vessel formation.
- The precise signal transduction pathways downstream of VEGF, particularly involving the VEGF receptor 2 (VEGFR2), are not fully elucidated.
- Understanding these pathways is critical for therapeutic interventions targeting angiogenesis in diseases like cancer and ischemic disorders.
Purpose of the Study:
- To investigate the role of Hippo pathway effectors, Yes-associated protein (YAP) and Tafazzin (TAZ), in mediating VEGF signaling during angiogenesis.
- To elucidate the molecular mechanisms by which YAP/TAZ regulate vascular development and VEGFR2 signaling.
- To determine the necessity of YAP/TAZ for proper vascularization and embryonic development.
Main Methods:
- Endothelium-specific gene deletion of YAP and TAZ in mouse models.
- Analysis of vascular development and embryonic lethality.
- Biochemical and cellular assays to study VEGF-induced signaling, actin cytoskeleton dynamics, and protein trafficking.
- Transcriptional profiling to identify YAP/TAZ-regulated genes.
Main Results:
- Endothelium-specific deletion of YAP/TAZ resulted in severe defects in vascularization and embryonic lethality, highlighting their essential role in vascular development.
- VEGF signaling activates YAP/TAZ through modulation of the actin cytoskeleton.
- Activated YAP/TAZ induce a transcriptional program that reinforces cytoskeleton dynamics, creating a positive feedback loop for angiogenesis.
- Loss of YAP/TAZ led to impaired trafficking of VEGFR2 from the Golgi apparatus to the plasma membrane, affecting receptor localization and signaling.
Conclusions:
- YAP and TAZ act as central signal transducers for VEGF-VEGFR2 signaling in the endothelium.
- YAP/TAZ are essential regulators of angiogenesis by controlling cytoskeleton dynamics and receptor trafficking.
- This study identifies YAP/TAZ as critical mediators of vascular development and potential therapeutic targets for angiogenesis-related diseases.
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