Putting VE-cadherin into JAIL for junction remodeling

Cao, Jiahui; Schnittler, Hans-Joachim

doi:10.1242/jcs.222893

Cited by 36 publications

(38 citation statements)

References 199 publications

(266 reference statements)

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“…Tie-2 and S1P 1 stabilize endothelial junctions by modulating actomyosin fiber tension of radial stress fibers and circumferential actin via the regulation of Rac1, Cdc42, and Rho ( Mammoto et al, 2007 ; Wang and Dudek, 2009 ; David et al, 2011 ; Frye et al, 2015 ; Braun et al, 2019 ). In addition, actin polymerization and dynamics regulate junction formation and stability ( Cao and Schnittler, 2019 ).…”

Section: Adhesion Molecules Which Regulate the Barrier Function Of Blmentioning

confidence: 99%

Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin

Duong

Vestweber

2020

Front. Physiol.

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Endothelial junctions provide blood and lymph vessel integrity and are essential for the formation of a vascular system. They control the extravasation of solutes, leukocytes and metastatic cells from blood vessels and the uptake of fluid and leukocytes into the lymphatic vascular system. A multitude of adhesion molecules mediate and control the integrity and permeability of endothelial junctions. VE-cadherin is arguably the most important adhesion molecule for the formation of vascular structures, and the stability of their junctions. Interestingly, despite this prominence, its elimination from junctions in the adult organism has different consequences in the vasculature of different organs, both for blood and lymph vessels. In addition, even in tissues where the lack of VE-cadherin leads to strong plasma leaks from venules, the physical integrity of endothelial junctions is preserved. Obviously, other adhesion molecules can compensate for a loss of VEcadherin and this review will discuss which other adhesive mechanisms contribute to the stability and regulation of endothelial junctions and cooperate with VE-cadherin in intact vessels. In addition to adhesion molecules, endothelial receptors will be discussed, which stimulate signaling processes that provide junction stability by modulating the actomyosin system, which reinforces tension of circumferential actin and dampens pulling forces of radial stress fibers. Finally, we will highlight most recent reports about the formation and control of the specialized button-like junctions of initial lymphatics, which represent the entry sites for fluid and cells into the lymphatic vascular system.

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Section: Adhesion Molecules Which Regulate the Barrier Function Of Blmentioning

confidence: 99%

Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin

Duong

Vestweber

2020

Front. Physiol.

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“…Actin disruption would also affect local processes at inter cellular adhesions, such as VEcadherin recycling and clustering that regulate intercellular adhesion (Cao et al, 2019). We thus used fluorescence photobleaching after recovery (FRAP) measurements to determine whether observed changes in actin and energy depletion also results in local changes at junctions.…”

Section: Inhibiting Glycolysis Reduces the Diffusivity And Mobile Framentioning

confidence: 99%

Glycolysis Inhibition Regulates Endothelial Junctions by Perturbing Actin and Focal Adhesions

Schwarz

Gajwani

Rehman

et al. 2020

Preprint

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One of the central functions of the endothelium is to maintain a vascular barrier that prevents fluid leakiness and immune cell influx from the circulating blood into the tissue. The barrier integrity of the endothelium is largely controlled by adherens junctions (AJs) and the key AJ molecule VE-cadherin, which maintains cell cohesion via homotypic trans-interaction with VE-cadherin molecules on neighboring endothelial cells. Tension is required to maintain junction homeostasis, but little is known about the role of endothelial metabolism and bioenergetics in regulating junctional forces. Because glycolysis is the main source of ATP generation in endothelial cells, we examined the bioenergetic control of the mechanics of VE-cadherin junctions, by focusing on the glycolysis regulatory enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Results from traction force imbalance measurements and a VE-cadherin tension sensor revealed that inhibiting PFKFB3 significantly reduced the average junctional tension and the force on VE-cadherin complexes. The decrease in tension was largely due to mechanical changes distal from the cell-cell contacts. Specifically, inhibiting glycolysis perturbs focal adhesions and disrupts actin organization, directly impacting the net force on intercellular contacts. These findings identify a critical role of cellular metabolism for the mechanics and integrity of vascular endothelial junctions, by maintaining global cell mechanics.

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“…The formation of new blood vessels through angiogenesis involves endothelial cell (EC) adhesion, migration and proliferation and is critical for embryo development and tissue regeneration (Potente et al, 2011). Angiogenesis relies on the dynamic rearrangement of VE-cadherin (VEcad)mediated cell-cell junctions (Giannotta et al, 2013;Cao and Schnittler, 2019). Endothelial cell-cell junctions are also crucial for vessel permeability, vessel stability and vascular integrity (Dejana et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The VEcad-catenin complex, which constitute the molecular basis of the adherens junctions, is connected to the actin cytoskeleton and its function is regulated by signal transduction, cytoskeletal contraction, and actin-driven plasma membrane protrusions (Dejana and Vestweber, 2013;Giannotta et al, 2013;Cao et al, 2017;Paatero et al, 2018;Cao and Schnittler, 2019). Endothelial adherens junctions are highly dynamic and therefore require constant VEcad rearrangement (Bentley et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Coronin 1B Controls Endothelial Actin Dynamics at Cell–Cell Junctions and Is Required for Endothelial Network Assembly

Werner¹,

Weckbach²,

Salvermoser³

et al. 2020

Front. Cell Dev. Biol.

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Development and homeostasis of blood vessels critically depend on the regulation of endothelial cell-cell junctions. VE-cadherin (VEcad)-based cell-cell junctions are connected to the actin cytoskeleton and regulated by actin-binding proteins. Coronin 1B (Coro1B) is an actin binding protein that controls actin networks at classical lamellipodia. The role of Coro1B in endothelial cells (ECs) is not fully understood and investigated in this study. Here, we demonstrate that Coro1B is a novel component and regulator of cell-cell junctions in ECs. Immunofluorescence studies show that Coro1B colocalizes with VEcad at cell-cell junctions in monolayers of ECs. Live-cell imaging reveals that Coro1B is recruited to, and operated at actin-driven membrane protrusions at cellcell junctions. Coro1B is recruited to cell-cell junctions via a mechanism that requires the relaxation of the actomyosin cytoskeleton. By analyzing the Coro1B interactome, we identify integrin-linked kinase (ILK) as new Coro1B-associated protein. Coro1B colocalizes with α-parvin, an interactor of ILK, at the leading edge of lamellipodia protrusions. Functional experiments reveal that depletion of Coro1B causes defects in the actin cytoskeleton and cell-cell junctions. Finally, in matrigel tube network assays, depletion of Coro1B results in reduced network complexity, tube number and tube length. Together, our findings point toward a critical role for Coro1B in the dynamic remodeling of endothelial cell-cell junctions and the assembly of endothelial networks.

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Putting VE-cadherin into JAIL for junction remodeling

Cited by 36 publications

References 199 publications

Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin

Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin

Glycolysis Inhibition Regulates Endothelial Junctions by Perturbing Actin and Focal Adhesions

Coronin 1B Controls Endothelial Actin Dynamics at Cell–Cell Junctions and Is Required for Endothelial Network Assembly

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