The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions

Yvonne L. Dorland, Tsveta S. Malinova, Anne-Marieke D. van Stalborch, Adam G. Grieve, Daphne van Geemen, Nicolette S. Jansen, Bart-Jan de Kreuk, Kalim Nawaz, Jeroen Kole, Dirk Geerts, Rene J. P. Musters, Johan de Rooij, Peter L. Hordijk, Stephan Huveneers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Vascular homoeostasis, development and disease critically depend on the regulation of endothelial cell-cell junctions. Here we uncover a new role for the F-BAR protein pacsin2 in the control of VE-cadherin-based endothelial adhesion. Pacsin2 concentrates at focal adherens junctions (FAJs) that are experiencing unbalanced actomyosin-based pulling. FAJs move in response to differences in local cytoskeletal geometry and pacsin2 is recruited consistently to the trailing end of fast-moving FAJs via a mechanism that requires an intact F-BAR domain. Photoconversion, photobleaching, immunofluorescence and super-resolution microscopy reveal polarized dynamics, and organization of junctional proteins between the front of FAJs and their trailing ends. Interestingly, pacsin2 recruitment inhibits internalization of the VE-cadherin complex from FAJ trailing ends and is important for endothelial monolayer integrity. Together, these findings reveal a novel junction protective mechanism during polarized trafficking of VE-cadherin, which supports barrier maintenance within dynamic endothelial tissue.

Original languageEnglish
Article number12210
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 15 Jul 2016

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