Faculty Opinions recommendation of A non-canonical Notch complex regulates adherens junctions and vascular barrier function.

2017 ◽  
Author(s):  
Martin A Schwartz
Keyword(s):  
Barrier Function ◽  
Adherens Junctions

Effect of p18 on Endothelial Barrier Function by Mediating Vascular Endothelial Rab11a-VE-cadherin Recycling

2021 ◽  
Author(s):  
Bo-Wen Xu ◽  
Zhi-Qiang Cheng ◽  
Xu-Ting Zhi ◽  
Xiao-Mei Yang ◽  
Zhi-Bo Yan
Keyword(s):  
Barrier Function ◽  
Adherens Junctions ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Barrier Dysfunction ◽  
Recycling Endosome

Abstract Endothelial barrier integrity requires recycling of VE-cadherin to adherens junctions. Both p18 and Rab11a play significant roles in VE-cadherin recycling. However, the underlying mechanism and the role of p18 in activating Rab11a have yet to be elucidated. Performing in vitro and in vivo experiments, we showed that p18 protein bound to VE-cadherin before Rab11a through its VE-cadherin-binding domain (aa 1–39). Transendothelial resistance showed that overexpression of p18 promoted the circulation of VE-cadherin to adherens junctions and the recovery of the endothelial barrier. Silencing of p18 caused endothelial barrier dysfunction and prevented Rab11a-positive recycling endosome accumulation in the perinuclear recycling compartments. Furthermore, p18 knockdown in pulmonary microvessels markedly increased vascular leakage in mice challenged with lipopolysaccharide and cecal ligation puncture. This study showed that p18 regulated the pulmonary endothelial barrier function in vitro and in vivo by regulating the binding of Rab11a to VE-cadherin and the activation of Rab11a.

scholarly journals Phospholipase D2 restores endothelial barrier function by promoting PTPN14-mediated VE-cadherin dephosphorylation

2020 ◽  
Vol 295 (22) ◽  
pp. 7669-7685 ◽  
Author(s):  
Panfeng Fu ◽  
Ramaswamy Ramchandran ◽  
Mark Shaaya ◽  
Longshuang Huang ◽  
David L. Ebenezer ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protein Tyrosine Phosphatase ◽  
Barrier Function ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Protein Tyrosine ◽  
Adhesion Junctions

Increased permeability of vascular lung tissues is a hallmark of acute lung injury and is often caused by edemagenic insults resulting in inflammation. Vascular endothelial (VE)-cadherin undergoes internalization in response to inflammatory stimuli and is recycled at cell adhesion junctions during endothelial barrier re-establishment. Here, we hypothesized that phospholipase D (PLD)-generated phosphatidic acid (PA) signaling regulates VE-cadherin recycling and promotes endothelial barrier recovery by dephosphorylating VE-cadherin. Genetic deletion of PLD2 impaired recovery from protease-activated receptor-1–activating peptide (PAR-1–AP)-induced lung vascular permeability and potentiated inflammation in vivo. In human lung microvascular endothelial cells (HLMVECs), inhibition or deletion of PLD2, but not of PLD1, delayed endothelial barrier recovery after thrombin stimulation. Thrombin stimulation of HLMVECs increased co-localization of PLD2-generated PA and VE-cadherin at cell-cell adhesion junctions. Inhibition of PLD2 activity resulted in prolonged phosphorylation of Tyr-658 in VE-cadherin during the recovery phase 3 h post-thrombin challenge. Immunoprecipitation experiments revealed that after HLMVECs are thrombin stimulated, PLD2, VE-cadherin, and protein-tyrosine phosphatase nonreceptor type 14 (PTPN14), a PLD2-dependent protein-tyrosine phosphatase, strongly associate with each other. PTPN14 depletion delayed VE-cadherin dephosphorylation, reannealing of adherens junctions, and barrier function recovery. PLD2 inhibition attenuated PTPN14 activity and reversed PTPN14-dependent VE-cadherin dephosphorylation after thrombin stimulation. Our findings indicate that PLD2 promotes PTPN14-mediated dephosphorylation of VE-cadherin and that redistribution of VE-cadherin at adherens junctions is essential for recovery of endothelial barrier function after an edemagenic insult.

Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines

2003 ◽  
Vol 285 (5) ◽  
pp. C1174-C1187 ◽  
Author(s):  
Xin Guo ◽  
Jaladanki N. Rao ◽  
Lan Liu ◽  
Tong-Tong Zou ◽  
Douglas J. Turner ◽  
...  
Keyword(s):  
Barrier Function ◽  
Adherens Junctions ◽  
Critical Role ◽  
Intercellular Junctions ◽  
Paracellular Permeability ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Cell Functions ◽  
E Cadherin

Maintenance of intestinal mucosal epithelial integrity requires polyamines that are involved in the multiple signaling pathways controlling gene expression and different epithelial cell functions. Integrity of the intestinal epithelial barrier depends on a complex of proteins composing different intercellular junctions, including tight junctions, adherens junctions, and desmosomes. E-cadherin is primarily found at the adherens junctions and plays a critical role in cell-cell adhesions that are fundamental to formation of the intestinal epithelial barrier. The current study determined whether polyamines regulate intestinal epithelial barrier function by altering E-cadherin expression. Depletion of cellular polyamines by α-difluoromethylornithine (DFMO) reduced intracellular free Ca2+ concentration ([Ca2+]cyt), decreased E-cadherin expression, and increased paracellular permeability in normal intestinal epithelial cells (IEC-6 line). Polyamine depletion did not alter expression of tight junction proteins such as zona occludens (ZO)-1, ZO-2, and junctional adhesion molecule (JAM)-1. Addition of exogenous polyamine spermidine reversed the effects of DFMO on [Ca2+]cyt and E-cadherin expression and restored paracellular permeability to near normal. Elevation of [Ca2+]cyt by the Ca2+ ionophore ionomycin increased E-cadherin expression in polyamine-deficient cells. In contrast, reduction of [Ca2+]cyt by polyamine depletion or removal of extracellular Ca2+ not only inhibited expression of E-cadherin mRNA but also decreased the half-life of E-cadherin protein. These results indicate that polyamines regulate intestinal epithelial paracellular barrier function by altering E-cadherin expression and that polyamines are essential for E-cadherin expression at least partially through [Ca2+]cyt.

scholarly journals The tyrosine phosphatase SHP2 regulates recovery of endothelial adherens junctions through control of β-catenin phosphorylation

2012 ◽  
Vol 23 (21) ◽  
pp. 4212-4225 ◽  
Author(s):  
Ilse Timmerman ◽  
Mark Hoogenboezem ◽  
Anton M. Bennett ◽  
Dirk Geerts ◽  
Peter L. Hordijk ◽  
...  
Keyword(s):  
Barrier Function ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Endothelial Permeability ◽  
Cell Junctions ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Src Homology 2 Domain ◽  
Cell Cell

Impaired endothelial barrier function results in a persistent increase in endothelial permeability and vascular leakage. Repair of a dysfunctional endothelial barrier requires controlled restoration of adherens junctions, comprising vascular endothelial (VE)-cadherin and associated β-, γ-, α-, and p120-catenins. Little is known about the mechanisms by which recovery of VE-cadherin–mediated cell–cell junctions is regulated. Using the inflammatory mediator thrombin, we demonstrate an important role for the Src homology 2-domain containing tyrosine phosphatase (SHP2) in mediating recovery of the VE-cadherin–controlled endothelial barrier. Using SHP2 substrate-trapping mutants and an in vitro phosphatase activity assay, we validate β-catenin as a bona fide SHP2 substrate. SHP2 silencing and SHP2 inhibition both result in delayed recovery of endothelial barrier function after thrombin stimulation. Moreover, on thrombin challenge, we find prolonged elevation in tyrosine phosphorylation levels of VE-cadherin–associated β-catenin in SHP2-depleted cells. No disassembly of the VE-cadherin complex is observed throughout the thrombin response. Using fluorescence recovery after photobleaching, we show that loss of SHP2 reduces the mobility of VE-cadherin at recovered cell–cell junctions. In conclusion, our data show that the SHP2 phosphatase plays an important role in the recovery of disrupted endothelial cell–cell junctions by dephosphorylating VE-cadherin–associated β-catenin and promoting the mobility of VE-cadherin at the plasma membrane.

scholarly journals Adherens Junctions, Desmosomes and Tight Junctions in Epidermal Barrier Function

2010 ◽  
Vol 4 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Johanna M. Brandner ◽  
Marek Haftek ◽  
Carien M. Niessen
Keyword(s):  
Tight Junctions ◽  
Barrier Function ◽  
Adherens Junctions ◽  
Epidermal Barrier

scholarly journals Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells

2017 ◽  
Vol 28 (15) ◽  
pp. 2023-2034 ◽  
Author(s):  
Tomohito Higashi ◽  
Ann L. Miller
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Barrier Function ◽  
Hot Spots ◽  
Adherens Junctions ◽  
New Model ◽  
Open Questions ◽  
And Function ◽  
Molecular Components

Tricellular contacts are the places where three cells meet. In vertebrate epithelial cells, specialized structures called tricellular tight junctions (tTJs) and tricellular adherens junctions (tAJs) have been identified. tTJs are important for the maintenance of barrier function, and disruption of tTJ proteins contributes to familial deafness. tAJs have recently been attracting the attention of mechanobiologists because these sites are hot spots of epithelial tension. Although the molecular components, regulation, and function of tTJs and tAJs, as well as of invertebrate tricellular junctions, are beginning to be characterized, many questions remain. Here we broadly cover what is known about tricellular junctions, propose a new model for tension transmission at tAJs, and discuss key open questions.

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