VE-cadherin endocytosis controls vascular integrity and patterning during development

Cynthia M. Grimsley-Myers, Robin H. Isaacson, Chantel M. Cadwell, Jazmin Campos, Marina S. Hernandes, Kenneth R. Myers, Tadahiko Seo, William Giang, Kathy K. Griendling, Andrew P. Kowalczyk

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere201909081
JournalJournal of Cell Biology
Volume219
Issue number5
DOIs
StatePublished - May 4 2020

All Science Journal Classification (ASJC) codes

  • Cell Biology

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