EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin

Taha, Muna; Aldirawi, Mohammed; März, Sigrid; Seebach, Jochen; Odenthal-Schnittler, Maria; Bondareva, Olga; Bojovic, Vesna; Schmandra, T. C.; Wirth, Benedikt; Miętkowska, Magdalena; Rottner, Klemens; Schnittler, Hans

doi:10.1016/j.celrep.2019.09.043

Cited by 33 publications

(51 citation statements)

References 70 publications

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“…EPLIN (epithelial protein lost in neoplasm), which is an actin-and α-catenin-binding protein (Maul and Chang, 1999), has been shown to link actin filaments to adherens junctions in both epithelium and endothelium. In endothelium, EPLIN isoforms were shown to control actin dynamics in an isotype-specific manner, which directly impacts adherens junction dynamics and function (Abe and Takeichi, 2008;Chervin-Pétinot et al, 2012;Taha et al, 2019). It should also be mentioned that VE-cadherin is further associated with vimentin intermediary filaments via association with plakoglobin (γ-catenin); however, the functional role γ-catenin plays in this association is not completely understood.…”

Section: Adherens Junctions In Vascular Endotheliummentioning

confidence: 99%

“…By expression of actin-binding and cell junction molecules such as VE-cadherin-mCherry or -EGFP, subunits of the ARP2/3 complex (EGFP-p20) or LifeAct-EGFP in ECs, our research team documented that the actin-driven protrusions lead directly to new VE-cadherin adhesions. This process occurs at a junction size between 1 and 5 µm in time frames of 5 min (Abu Taha et al, 2014;Seebach et al, 2015;Cao et al, 2017;Taha et al, 2019). Since JAIL formation is a continuous process that leads to new VE-cadherin adhesions, VE-cadherin dynamics is also subject to permanent remodeling.…”

Section: Junction Associated Intermittent Lamellipodia (Jail)mentioning

confidence: 99%

“…Relative cell displacements and migration become more complex during endothelial sheet migration, as occurs in angiogenesis and wound healing. Under these conditions, some cells even migrate in opposite directions (Cao et al, 2017;Taha et al, 2019); however, the entire monolayer remains intact. In particular, the interaction of two adjacent cells in a monolayer, might appear to occur at a length of several dozen microns.…”

Section: Subjunctional Regulation By Jail Allows Multitasking Controlmentioning

confidence: 99%

“…These JAIL overlap adjacent cells and it is only in this area that interactions of VE-cadherin molecules can occur, which diffuse freely in the plasma membrane and form a structure known as a "VE-cadherin plaque (Figure 1)." Subsequently, after actin filaments have been depolymerized at the protrusion front [e.g., by EPLIN-a-mediated blockade of the ARP2/3 complex (Taha et al, 2019)], JAIL retract and VE-cadherin molecules of the plaques cluster together and become incorporated into junctions, thereby closing gaps or restoring insufficient/weak areas of cell junctions (Abu Taha et al, 2014).…”

Section: Subjunctional Regulation By Jail Allows Multitasking Controlmentioning

confidence: 99%

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Autoregulatory “Multitasking” at Endothelial Cell Junctions by Junction-Associated Intermittent Lamellipodia Controls Barrier Properties

2021

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Vascular endothelial cell (EC) junctions are key structures controlling tissue homeostasis in physiology. In the last three decades, excellent studies have addressed many aspects of this complex and highly dynamic regulation, including cell signaling, remodeling processes of the proteins of tight junctions, adherens junctions, and gap junctions, the cytoskeleton, and post-transcriptional modifications, transcriptional activation, and gene silencing. In this dynamic process, vascular endothelial cadherin (VE-cadherin) provides the core structure of EC junctions mediating the physical adhesion of cells as well as the control of barrier function and monolayer integrity via remodeling processes, regulation of protein expression and post-translational modifications. In recent years, research teams have documented locally restricted dynamics of EC junctions in which actin-driven protrusions in plasma membranes play a central role. In this regard, our research group showed that the dynamics of VE-cadherin is driven by small (1–5 μm) actin-mediated protrusions in plasma membranes that, due to this specific function, were named “junction-associated intermittent lamellipodia” (JAIL). JAIL form at overlapping, adjacent cells, and exactly at this site new VE-cadherin interactions occur, leading to new VE-cadherin adhesion sites, a process that restores weak or lost VE-cadherin adhesion. Mechanistically, JAIL formation occurs locally restricted (1–5 μm) and underlies autoregulation in which the local VE-cadherin concentration is an important parameter. A decrease in the local concentration of VE-cadherin stimulates JAIL formation, whereas an increase in the concentration of VE-cadherin blocks it. JAIL mediated VE-cadherin remodeling at the subjunctional level have been shown to be of crucial importance in angiogenesis, wound healing, and changes in permeability during inflammation. The concept of subjunctional regulation of EC junctions is strongly supported by permeability assays, which can be employed to quantify actin-driven subjunctional changes. In this brief review, we summarize and discuss the current knowledge and concepts of subjunctional regulation in the endothelium.

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Section: Adherens Junctions In Vascular Endotheliummentioning

confidence: 99%

Section: Junction Associated Intermittent Lamellipodia (Jail)mentioning

confidence: 99%

Section: Subjunctional Regulation By Jail Allows Multitasking Controlmentioning

confidence: 99%

Section: Subjunctional Regulation By Jail Allows Multitasking Controlmentioning

confidence: 99%

See 2 more Smart Citations

Autoregulatory “Multitasking” at Endothelial Cell Junctions by Junction-Associated Intermittent Lamellipodia Controls Barrier Properties

2021

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“…Actin-binding proteins regulate actin cytoskeleton dynamics thereby controlling the remodeling of endothelial cell-cell junctions, cell migration and vessel integrity (Pollard et al, 2000;Edwards et al, 2014). Several actin-binding proteins including EPLIN and α-parvin (α-pv) colocalize with and control JAIL formation (Fraccaroli et al, 2015;Taha et al, 2019). Parvins are a family of adaptor proteins that localize to focal complexes and focal adhesions, and facilitate the interaction of integrins with the actin cytoskeleton (Olski et al, 2001;Legate et al, 2006).…”

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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A passive pump‐assisted microfluidic assay for quantifying endothelial wound healing in response to fluid shear stress

Yang

et al. 2022

Electrophoresis

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There as an urgent need to quantify the endothelial wound-healing process in response to fluid shear stress to improve the biological and clinical understanding of healing mechanisms, which is of great importance for preventing healing impairment, chronic wounds, and postoperative in-stent restenosis. However, current experimental platforms not only require expensive, cumbersome, and powered pumping devices (to, e.g., generate cell scratches and load shear stress stimulation) but also lack quantitative controls for quantitative analysis. In this paper, a passive pump-assisted microfluidic assay is developed to quantify endothelial wound healing in response to fluid shear stress. Our assay consists of passive constant-flow pumps based on the siphon principle and a three-inlet microfluidic chip for cell wound-healing experiments. We also propose a method for quantitatively adjusting cell scratch size by controlling trypsin flow. Both numerical simulations and fluorescein experiments validate the effectiveness of this method. Moreover, we use the designed microfluidic assay to successfully generate cell scratches, load a 12-h shear stress of 5 dyn/cm 2 to the cells, and observe wound healing. The results indicate that the healing of a cell scratch is significantly accelerated under the stimulation of shear stress. In conclusion, our passive pump-assisted microfluidic assay shows versatility, applicability, and the potential for quantifying endothelial wound healing in response to fluid shear stress.

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EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin

Cited by 33 publications

References 70 publications

Autoregulatory “Multitasking” at Endothelial Cell Junctions by Junction-Associated Intermittent Lamellipodia Controls Barrier Properties

Autoregulatory “Multitasking” at Endothelial Cell Junctions by Junction-Associated Intermittent Lamellipodia Controls Barrier Properties

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

A passive pump‐assisted microfluidic assay for quantifying endothelial wound healing in response to fluid shear stress

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