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VE-cadherin endocytosis controls vascular integrity and patterning during development.
- Source :
-
The Journal of cell biology [J Cell Biol] 2020 May 04; Vol. 219 (5). - Publication Year :
- 2020
-
Abstract
- Tissue morphogenesis requires dynamic intercellular contacts that are subsequently stabilized as tissues mature. The mechanisms governing these competing adhesive properties are not fully understood. Using gain- and loss-of-function approaches, we tested the role of p120-catenin (p120) and VE-cadherin (VE-cad) endocytosis in vascular development using mouse mutants that exhibit increased (VE-cadGGG/GGG) or decreased (VE-cadDEE/DEE) internalization. VE-cadGGG/GGG mutant mice exhibited reduced VE-cad-p120 binding, reduced VE-cad levels, microvascular hemorrhaging, and decreased survival. By contrast, VE-cadDEE/DEE mutants exhibited normal vascular permeability but displayed microvascular patterning defects. Interestingly, VE-cadDEE/DEE mutant mice did not require endothelial p120, demonstrating that p120 is dispensable in the context of a stabilized cadherin. In vitro, VE-cadDEE mutant cells displayed defects in polarization and cell migration that were rescued by uncoupling VE-cadDEE from actin. These results indicate that cadherin endocytosis coordinates cell polarity and migration cues through actin remodeling. Collectively, our results indicate that regulated cadherin endocytosis is essential for both dynamic cell movements and establishment of stable tissue architecture.<br /> (© 2020 Grimsley-Myers et al.)
- Subjects :
- Actins genetics
Animals
Aorta growth & development
Aorta metabolism
Blood Vessels metabolism
Body Patterning genetics
Cell Movement genetics
Cell Polarity genetics
Embryo, Mammalian
Endocytosis genetics
Endothelium, Vascular metabolism
Mice
Protein Binding genetics
Delta Catenin
Antigens, CD genetics
Blood Vessels growth & development
Cadherins genetics
Catenins genetics
Embryonic Development genetics
Endothelium, Vascular growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 219
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 32232465
- Full Text :
- https://doi.org/10.1083/jcb.201909081