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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.<\/jats:p>","DOI":"10.1083\/jcb.201909081","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T02:21:47Z","timestamp":1582942907000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["VE-cadherin endocytosis controls vascular integrity and patterning during development"],"prefix":"10.1083","volume":"219","author":[{"given":"Cynthia M.","family":"Grimsley-Myers","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin H.","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantel M.","family":"Cadwell","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9384-9913","authenticated-orcid":true,"given":"Jazmin","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-1441","authenticated-orcid":true,"given":"Marina S.","family":"Hernandes","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-2643","authenticated-orcid":true,"given":"Kenneth R.","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiko","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-259X","authenticated-orcid":true,"given":"William","family":"Giang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy K.","family":"Griendling","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6438-7863","authenticated-orcid":true,"given":"Andrew P.","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Department of Dermatology, and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"2023072407170710700_bib1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.cub.2009.02.057","article-title":"VE-Cadherin-mediated cell-cell interaction suppresses sprouting via signaling to MLC2 phosphorylation","volume":"19","author":"Abraham","year":"2009","journal-title":"Curr. 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