VE-cadherin at a glance

Bravi, Luca; Dejana, Elisabetta; Lampugnani, Maria Grazia

doi:10.1007/s00441-014-1843-7

Cited by 42 publications

(38 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both junction types are functionally linked with the cortical actin cytoskeleton through several adaptor molecules. Therefore, intracellular signaling affecting actin dynamics is essential in regulating endothelial barrier function 7–10 .…”

Section: Introductionmentioning

confidence: 99%

Histamine causes endothelial barrier disruption via Ca2+-mediated RhoA activation and tension at adherens junctions

Kugelmann

Rotkopf

Radeva

et al. 2018

Sci Rep

View full text Add to dashboard Cite

During inflammation, the disruption of the endothelial barrier leads to increased microvascular permeability. Whether tension along cell junctions contributes to histamine-induced endothelial barrier disruption remains unknown. Rapid Ca2+ influx induced by both histamine and thrombin was accompanied by endothelial barrier breakdown revealed as drop of transendothelial electric resistance in primary human microvascular endothelial cells. Interestingly, GLISA measurements revealed activation of RhoA but not inactivation of Rac1 at the time-point of barrier breakdown. FRET measurements showed activation of RhoA at intercellular junctions after both thrombin and histamine exposure. Breakdown coincided with increased stress fiber formation but not with translocation of vinculin, which was located along junctions in the resting state similar to postcapillary venules ex vivo. Moreover, increased tension at AJs was indicated by immunostaining with a conformation-sensitive antibody targeting the α18-subunit of α-catenin. Ca2+ chelation by BAPTA-AM and ROCK1 inhibition by Y27632 abolished both increase of tension along AJs as well as barrier dysfunction. Moreover, BAPTA-AM decreased RhoA activation following histamine stimulation, indicating a key role of Ca2+ signaling in barrier breakdown. Taken together, in response to histamine, Ca2+ via RhoA/ROCK activation along endothelial adherens junctions (AJs) appears to be critical for barrier disruption and presumably correlated with enhanced tension. However, vinculin appears not to be critical in this process.

show abstract

Section: Introductionmentioning

confidence: 99%

Histamine causes endothelial barrier disruption via Ca2+-mediated RhoA activation and tension at adherens junctions

Kugelmann

Rotkopf

Radeva

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The canonical growth factor VEGF after binding to VEGFR2 induces EC migration, recruitment, and proliferation 6 . The stability of VE-cadherin homotypic interaction at adherens junctions (AJs) is maintained by its association with cytoplasmic catenin proteins α-, β-, γ-and p120-catenins, which anchor VE-cadherin to the actin cytoskeleton 7 .…”

Section: Introductionmentioning

confidence: 99%

Novel Role of Reactive Oxygen Species–Activated trp Melastatin Channel-2 in Mediating Angiogenesis and Postischemic Neovascularization

Mittal

Urao

Hecquet

et al. 2015

ATVB

View full text Add to dashboard Cite

Objective Transient Receptor Potential Melastatin-2 (TRPM2) channel is a non-selective cation channel that mediates influx of Ca2+ and Na+ with relative permeability of PCa:PNa ∼0.6 in response to cellular oxidative stress. As angiogenesis and ischemic neovascularization are both significantly dependent on oxidant signaling, here we investigated the possibile role of VEGF-induced ROS production in activating TRPM2-dependent Ca2+ signaling, and in the mechanism of angiogensis and ischemic neovascularization. Approach and Results We observed that VEGF stimulation rapidly induced the association of TRPM2 and c-Src kinase with VE-cadherin forming a signalplex at VE-cadherin junctions in endothelial cells (ECs). Using ECs isolated from TRPM2−/− mice or after siRNA depletion of TRPM2, we demonstrated that TRPM2-activated Ca2+ signaling was required for c-Src kinase-induced phosphorylation of VE-cadherin at Y658 and Y731, the crucial sites involved in VE-cadherin internalization in response to VEGF. VEGF-induced ROS generation activated TRPM2-induced Ca2+ entry whereas the ROS-insensitive TRPM2 mutant (C1008→A) showed impaired Ca2+ entry. ECs depleted of TRPM2 also displayed significantly perturbed migratory phenotype and impaired activation of c-Src in response to VEGF. TRPM2-/- mice reconstituted with wild type myeloid cells demonstrated aberrant angiogenesis and neovascularisation in the hindlimb ischemia model as compared to wild type mice. Conclusion VEGF-induced angiogeneis and post-ischemic neovascularisation in mice required ROS generation in ECs and resultant TRPM2 activation. Thus, our findings provide novel insight into the role of TRPM2 in mechanism of angiogenesis and ischemic neovascularisation.

show abstract

“…It is strictly endothelial cell specific and constitutively expressed in all types of vessels including lymphatic vessels, arteries and veins [153,154]. Endothelial cells form a selective trans-and paracellular barrier controlling the passage of fluids, leukocytes and macromolecules between blood vessels and underlying tissue.…”

Section: Ve-cadherinmentioning

confidence: 99%