Visualization of Endothelial Actin Cytoskeleton in the Mouse Retina

Fraccaroli, Alessia; Franco, Cláudio A.; Rognoni, Emanuel; Neto, Filipa; Rehberg, Markus; Aszódi, Attila; Wedlich‐Söldner, Roland; Pohl, Ulrich; Gerhardt, Holger; Montañez, Eloi

doi:10.1371/journal.pone.0047488

Cited by 34 publications

(30 citation statements)

References 19 publications

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“…The LifeAct-GFP mouse expresses an actin-binding protein fused to eGFP that labels filamentous actin specifically (Riedl et al, 2010). Importantly, the LifeAct-GFP transgene is strongly expressed by the retinal endothelium, allowing visualization of the actin cytoskeleton specifically in the vasculature (Fraccaroli et al, 2012). By confocal microscopy, we observed a marked decrease in endothelial actin polymerization in SRF iEC-KO /LifeAct-GFP retinas in filopodia and at the filopodium base (Fig.…”

Section: Endothelial Actin Filament Organization Defects In Srfmentioning

confidence: 76%

SRF selectively controls tip cell invasive behavior in angiogenesis

et al. 2013

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SUMMARYEfficient angiogenic sprouting is essential for embryonic, postnatal and tumor development. Serum response factor (SRF) is known to be important for embryonic vascular development. Here, we studied the effect of inducible endothelial-specific deletion of Srf in postnatal and adult mice. We find that endothelial SRF activity is vital for postnatal growth and survival, and is equally required for developmental and pathological angiogenesis, including during tumor growth. Our results demonstrate that SRF is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis, but seems dispensable for vascular remodeling. At the molecular level, we observe that vascular endothelial growth factor A induces nuclear accumulation of myocardinrelated transcription factors (MRTFs) and regulates MRTF/SRF-dependent target genes including Myl9, which is important for endothelial cell migration in vitro. We conclude that SRF has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis. We hypothesize that targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth.

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Section: Endothelial Actin Filament Organization Defects In Srfmentioning

confidence: 76%

SRF selectively controls tip cell invasive behavior in angiogenesis

et al. 2013

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“…How such force-dependent junction remodeling relates to the function of vascular endothelial junctions in vivo is less clear, although recent advances have been made in studies that visualized the remodeling of endothelial cell–cell contacts and the actin cytoskeleton during angiogenesis and anastomosis in transgenic models [31, 32]. Importantly, temporal control of the interaction between F-actin and the VE-cadherin complex turns out to be crucial for agonist-evoked vascular permeability and leukocyte extravasation in adult mice [33].…”

Section: Mechanical Regulation Of Endothelial Cell–cell Junctionsmentioning

confidence: 99%

Cell–cell junctional mechanotransduction in endothelial remodeling

Dorland

Huveneers

2016

Cell. Mol. Life Sci.

135

142

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The vasculature is one of the most dynamic tissues that encounter numerous mechanical cues derived from pulsatile blood flow, blood pressure, activity of smooth muscle cells in the vessel wall, and transmigration of immune cells. The inner layer of blood and lymphatic vessels is covered by the endothelium, a monolayer of cells which separates blood from tissue, an important function that it fulfills even under the dynamic circumstances of the vascular microenvironment. In addition, remodeling of the endothelial barrier during angiogenesis and trafficking of immune cells is achieved by specific modulation of cell–cell adhesion structures between the endothelial cells. In recent years, there have been many new discoveries in the field of cellular mechanotransduction which controls the formation and destabilization of the vascular barrier. Force-induced adaptation at endothelial cell–cell adhesion structures is a crucial node in these processes that challenge the vascular barrier. One of the key examples of a force-induced molecular event is the recruitment of vinculin to the VE-cadherin complex upon pulling forces at cell–cell junctions. Here, we highlight recent advances in the current understanding of mechanotransduction responses at, and derived from, endothelial cell–cell junctions. We further discuss their importance for vascular barrier function and remodeling in development, inflammation, and vascular disease.

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“…Tip cells dynamically extend lamellipodia and filopodia that are composed of actin networks as they migrate during angiogenesis (Fraccaroli et al, 2012). Actin cytoskeleton remodeling requires large amounts of ATP, coupling actin polymerization with ATP hydrolysis (Pollard, 2007;Romero et al, 2007;Yogurtcu et al, 2012).…”

Section: Glycogen Metabolismmentioning

confidence: 99%

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

Stapor

Wang

Goveia

et al. 2014

Journal of Cell Science

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Clinically approved therapies that target angiogenesis in tumors and ocular diseases focus on controlling pro-angiogenic growth factors in order to reduce aberrant microvascular growth. Although research on angiogenesis has revealed key mechanisms that regulate tissue vascularization, therapeutic success has been limited owing to insufficient efficacy, refractoriness and tumor resistance. Emerging concepts suggest that, in addition to growth factors, vascular metabolism also regulates angiogenesis and is a viable target for manipulating the microvasculature. Recent studies show that endothelial cells rely on glycolysis for ATP production, and that the key glycolytic regulator 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase 3 (PFKFB3) regulates angiogenesis by controlling the balance of tip versus stalk cells. As endothelial cells acquire a tip cell phenotype, they increase glycolytic production of ATP for sprouting. Furthermore, pharmacological blockade of PFKFB3 causes a transient, partial reduction in glycolysis, and reduces pathological angiogenesis with minimal systemic harm. Although further assessment of endothelial cell metabolism is necessary, these results represent a paradigm shift in anti-angiogenic therapy from targeting angiogenic factors to focusing on vascular metabolism, warranting research on the metabolic pathways that govern angiogenesis.

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Visualization of Endothelial Actin Cytoskeleton in the Mouse Retina

Cited by 34 publications

References 19 publications

SRF selectively controls tip cell invasive behavior in angiogenesis

SRF selectively controls tip cell invasive behavior in angiogenesis

Cell–cell junctional mechanotransduction in endothelial remodeling

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

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