Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction

Daneshjou, Nazila; Sieracki, Nathan A.; Amerongen, Geerten P. van Nieuw; Conway, Daniel E.; Schwartz, Martin A.; Komarova, Yulia; Malik, Asrar B.

doi:10.1083/jcb.201409108

Cited by 67 publications

(105 citation statements)

References 45 publications

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“…The role of VE‐cadherin is not clear but it most likely regulates the strength of adhesion between individual cells (Daneshjou et al , 2015). In addition, it has been recently shown to interact with VEGFR2 and VEGFR3 and Src kinases, which was hypothesized to facilitate phosphorylation of VEGFR2 and VEGFR3 (Coon et al , 2015) and thereby promote downstream signalling events.…”

Section: Introductionmentioning

confidence: 99%

Endothelial basement membrane laminin 511 is essential for shear stress response

Russo¹,

Luik²,

Yousif³

et al. 2016

The EMBO Journal

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Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM‐1 and VE‐cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin β1‐positive/vinculin‐positive focal adhesions, and reduced junctional association of actin–myosin II. In vitro assays reveal that β1 integrin‐mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE‐cadherin, stabilizing it at cell junctions and increasing cell–cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.

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Section: Introductionmentioning

confidence: 99%

Endothelial basement membrane laminin 511 is essential for shear stress response

Russo¹,

Luik²,

Yousif³

et al. 2016

The EMBO Journal

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“…Integrin activation and ligation to ECM is required for endothelial adaptation to shear stress through the activation of the Rho family GTPases Rac1, RhoA, and Cdc42 [36,37], which coordinate the cytoskeletal rearrangements required for cellular alignment to flow, inflammatory signaling, and presentation of apical cell-adhesion receptors [38]. Rac1 activity also serves to promote VE-Cadherin stability by locally counteracting actomysoin force on VE-cadherin trans-dimers [39]. Recent evidence suggests that the AJ mechanotransduction complex may be able to spatially control the activation of Rac1 through the local recruitment of the GEF Trio to VE-cadherin [40].…”

Section: Molecular Force Sensing and Mechanotransductionmentioning

confidence: 99%

Forces and mechanotransduction in 3D vascular biology

Kutys

Chen

2016

Current Opinion in Cell Biology

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The effects of hemodynamic and interstitial mechanical forces on endothelial biology in vivo have been appreciated for over half a century, regulating vessel network development, homeostatic function, and progression of vascular disease. Investigations using cultures of endothelial cells on two-dimensional (2D) substrates have elucidated important mechanisms by which microenvironmental stresses are sensed and transduced into chemical signaling responses. However recent studies in vivo and in three-dimensional (3D) in vitro models of vascular beds have enabled the investigation of forces and cellular behaviors previously not possible in traditional 2D culture systems. These studies support a developing paradigm that the 3D chemo-mechanical architecture of the vascular niche impacts how endothelial cells both sense and respond to microenvironmental forces. We present evolving concepts in endothelial force sensing and mechanical signaling and highlight recent insights gained from in vivo and 3D in vitro vascular models.

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“…However the nature of these effects can vary from system to system. For example, actomyosin based contractility can enhance junctional stability in some systems [19] and promote junctional turnover in other systems [20]. During Drosophila melanogaster gastrulation there is an apical enrichment of adherens junctions, which is lost if apical constriction is inhibited [19, 21], and during Xenopus gastrulation, myosin activity leads to altered C-cadherin dynamics [22].…”

Section: Introductionmentioning

confidence: 99%

MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation

et al. 2016

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Summary Apical constriction is a change in cell shape that drives key morphogenetic events including gastrulation and neural tube formation. Apical force-producing actomyosin networks drive apical constriction by contracting while connected to cell-cell junctions. The mechanisms by which developmental patterning regulates these actomyosin networks and associated junctions with spatial precision are not fully understood. Here, we identify a myosin light chain kinase MRCK-1 as a key regulator of C. elegans gastrulation that integrates spatial and developmental patterning information. We show that MRCK-1 is required for activation of contractile actomyosin dynamics and elevated cortical tension in the apical cell cortex of endodermal precursor cells. MRCK-1 is apically localized by active Cdc42 at the external, cell-cell contact-free surfaces of apically constricting cells, downstream of cell fate determination mechanisms. We establish that the junctional components α-catenin, β-catenin, and cadherin become highly enriched at the apical junctions of apically-constricting cells, and that MRCK-1 and myosin activity are required in vivo for this enrichment. Taken together, our results define mechanisms that position a myosin activator to a specific cell surface where it both locally increases cortical tension and locally enriches junctional components to facilitate apical constriction. These results reveal crucial links that can tie spatial information to local force generation to drive morphogenesis.

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Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction

Abstract: In endothelial cells, the RhoGTPase Rac1 stabilizes VE-cadherin trans-dimers in mature adherens junctions by counteracting actomyosin tension.

Cited by 67 publications

References 45 publications

Endothelial basement membrane laminin 511 is essential for shear stress response

Endothelial basement membrane laminin 511 is essential for shear stress response

Forces and mechanotransduction in 3D vascular biology

MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation

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