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VE-cadherin endocytosis controls vascular integrity and patterning during development
Cynthia M Grimsley-Myers1, Robin H Isaacson1, Chantel M Cadwell1
1Department of Cell Biology, Emory University School of Medicine, Atlanta, GA.
The Journal of Cell Biology
|April 2, 2020
Summary
Regulated endocytosis of vascular endothelial cadherin (VE-cad) is crucial for blood vessel development. Disrupting VE-cad internalization impacts cell migration, polarity, and tissue stability.
Area of Science:
- Cell Biology
- Developmental Biology
- Vascular Biology
Background:
- Tissue morphogenesis relies on dynamic cell-cell contacts that mature into stable structures.
- The precise mechanisms controlling the balance between dynamic and stable adhesion are not fully elucidated.
- Vascular endothelial cadherin (VE-cad) plays a critical role in endothelial cell adhesion and vascular development.
Purpose of the Study:
- To investigate the role of p120-catenin (p120) and VE-cad endocytosis in vascular development.
- To understand how altered cadherin endocytosis affects vascular integrity, cell polarity, and migration.
Main Methods:
- Utilized mouse mutants with altered VE-cad internalization (VE-cadGGG/GGG and VE-cadDEE/DEE).
- Employed gain- and loss-of-function approaches to study p120 and VE-cad.
- Performed in vitro experiments with mutant cells to assess polarization and migration.
Main Results:
- VE-cadGGG/GGG mutants showed reduced VE-cad-p120 binding, lower VE-cad levels, hemorrhaging, and decreased survival.
- VE-cadDEE/DEE mutants displayed normal vascular permeability but had microvascular patterning defects.
- p120 was dispensable in VE-cadDEE/DEE mutants, indicating its role is context-dependent on cadherin stabilization.
- In vitro, VE-cadDEE mutant cells showed impaired polarization and migration, rescued by uncoupling from actin.
Conclusions:
- Regulated cadherin endocytosis is essential for coordinating cell polarity and migration via actin remodeling.
- Controlled VE-cad endocytosis is vital for both dynamic cell movements during development and the establishment of stable tissue architecture.
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