Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization

Ando, Koji; Fukuhara, Shigetomo; Moriya, Takahiro; Obara, Yutaro; Nakahata, Norimichi; Mochizuki, Naoki

doi:10.1083/jcb.201301115

Cited by 130 publications

(173 citation statements)

References 59 publications

(108 reference statements)

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“…In endothelial cells, MRCK is activated upon induction of cell-cell contacts and controls how compact and aligned circumferential bundles are towards junctions [86]. However, in this model, Tuba is not involved, but a different GEF (FGD5) is recruited to activate Cdc42 and MRCK, thereby promoting linear endothelial junctions [86].…”

Section: Different Hues Of the Same Colourmentioning

confidence: 99%

“…A likely candidate is MRCK, a kinase effector of Cdc42, that associates with acto-myosin filaments and, similar to ROCKI/II, phosphorylates myosin regulatory chain [85]. In endothelial cells, MRCK is activated upon induction of cell-cell contacts and controls how compact and aligned circumferential bundles are towards junctions [86]. However, in this model, Tuba is not involved, but a different GEF (FGD5) is recruited to activate Cdc42 and MRCK, thereby promoting linear endothelial junctions [86].…”

Section: Different Hues Of the Same Colourmentioning

confidence: 99%

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Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

Braga

2016

Current Opinion in Cell Biology

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Section: Different Hues Of the Same Colourmentioning

confidence: 99%

Section: Different Hues Of the Same Colourmentioning

confidence: 99%

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

Braga

2016

Current Opinion in Cell Biology

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“…VE-cadherin promotes Rho-kinase activity, MLC phosphorylation and actomyosin contractility, which, in turn, enhances VE-cadherin accumulation at cell junctions and thereby vessel stability 33,34 . The small GTPase Rap1, another important regulator of endothelial junction formation 35 , has been recently shown to promote VE-cadherin-dependent cell-cell adhesion through Cdc42, the kinase MRCK, MLC phosphorylation and actin reorganization 36 .…”

Section: Inducible Inactivation Of Itgb1 In the Postnatal Endotheliummentioning

confidence: 99%

Integrin β1 controls VE-cadherin localization and blood vessel stability

et al. 2015

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Angiogenic blood vessel growth requires several distinct but integrated cellular activities. Endothelial cell sprouting and proliferation lead to the expansion of the vasculature and give rise to a highly branched, immature plexus, which is subsequently reorganized into a mature and stable network. Although it is known that integrin-mediated cell-matrix interactions are indispensable for embryonic angiogenesis, little is known about the function of integrins in different steps of vascular morphogenesis. Here, by investigating the integrin b1-subunit with inducible and endothelial-specific gene targeting in the postnatal mouse retina, we show that b1 integrin promotes endothelial sprouting but is a negative regulator of proliferation. In maturing vessels, integrin b1 is indispensable for proper localization of VE-cadherin and thereby cell-cell junction integrity. The sum of our findings establishes that integrin b1 has critical functions in the growing and maturing vasculature, and is required for the formation of stable, non-leaky blood vessels.

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“…As a follow up, the same group showed that Rap1 activates Cdc42 through the Rho-GEF FGD5. 81 This includes the local phosphorylation of myosin light chain (MLC) by the myotonic dystrophy-kinase related Cdc42-binding kinase (MRCK). Interestingly, a study by the Bos lab showed that Rap1 activation results in inhibition of RhoA activity, releasing tension from the junction region and thereby promoting stabilization of endothelial cell-cell junctions.…”

Section: Endothelial Adherens Junction Control By Rho Gtpasesmentioning

confidence: 99%

Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

Buul

Timmerman

2016

Small GTPases

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VE-cadherin-based cell-cell junctions form the major restrictive barrier of the endothelium to plasma proteins and blood cells. The function of VE-cadherin and the actin cytoskeleton are intimately linked. Vascular permeability factors and adherent leukocytes signal through small Rho GTPases to tightly regulate actin cytoskeletal rearrangements in order to open and re-assemble endothelial cell-cell junctions in a rapid and controlled manner. The Rho GTPases are activated by guanine nucleotide exchange factors (GEFs), conferring specificity and context-dependent control of cell-cell junctions. Although the molecular mechanisms that couple cadherins to actin filaments are beginning to be elucidated, specific stimulus-dependent regulation of the actin cytoskeleton at VEcadherin-based junctions remains unexplained. Accumulating evidence has suggested that depending on the vascular permeability factor and on the subcellular localization of GEFs, cell-cell junction dynamics and organization are differentially regulated by one specific Rho GTPase. In this Commentary, we focus on new insights how the junctional actin cytoskeleton is specifically and locally regulated by Rho GTPases and GEFs in the endothelium.

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Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization

Abstract: Rap1 potentiates endothelial cell junctions by spatially controlling non-muscle myosin II activity through activation of the Cdc42–MRCK pathway and suppression of the Rho–ROCK pathway.

Cited by 130 publications

References 59 publications

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

Integrin β1 controls VE-cadherin localization and blood vessel stability

Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

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