Septins regulate junctional integrity of endothelial monolayers

Molecular Biology of the Cell
Joanna Kim, John A Cooper

Abstract

Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions extending above or below neighboring cells. Vascular endothelial cadherin (VE-cadherin) was present at cell junctions, with a membrane-associated layer of F-actin. Septins localized at cell-junction membranes, in patterns distinct from VE-cadherin and F-actin. Septins assumed curved and scallop-shaped patterns at junctions, especially in regions of positive membrane curvature associated with actin-rich membrane protrusions. Depletion of septins led to disrupted morphology of VE-cadherin junctions and increased expression of VE-cadherin. In videos, septin-depleted cells displayed remodeling at cell junctions; regions with VE-cadherin were broader, and areas with membrane ruffling were wider. Septin depletion and junction disruption led to functional loss of junctional integrity, revealed by decreased transendothelial electric resistance and increased transmigration of immune cells. We conclude that septins, as cytoskel...Continue Reading

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Citations

Oct 4, 2018·Molecular Biology of the Cell·David S BoothNicole King
Nov 6, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Joanna Kim, John A Cooper
Oct 12, 2020·The American Journal of Pathology·Andrei I IvanovFlorian Rieder
Nov 14, 2020·Cytoskeleton·Barry T DeRoseShae B Padrick
Apr 14, 2021·ELife·Agata SzubaGijsje H Koenderink
May 26, 2021·Current Biology : CB·Elias T Spiliotis, Konstantinos Nakos
Jun 4, 2021·Molecular Biology of the Cell·Yekaterina A MiroshnikovaCorinne Albiges-Rizo

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Methods Mentioned

BETA
scanning electron microscopy
confocal microscopy
transmission electron microscopy
reverse transcription-PCR
PCR
scraping

Software Mentioned

ImageJ
GraphPad Prism

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