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Nat Commun. 2016 Jul 15;7:12210. doi: 10.1038/ncomms12210.

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

Author information

1
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam 1066 CX, The Netherlands.
2
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
3
Hubrecht Institute and University Medical Center Utrecht, Utrecht 3584 CT, The Netherlands.
4
Department of Medicine, University of California, San Diego, California 92093, USA.
5
Department of Physiology, VU University Medical Center, Amsterdam 1081 HV, The Netherlands.
6
Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, Rotterdam 3015 GE, The Netherlands.
7
Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.

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.

PMID:
27417273
PMCID:
PMC4947187
DOI:
10.1038/ncomms12210
[Indexed for MEDLINE]
Free PMC Article

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