A distinct PAR complex associates physically with VE‐cadherin in vertebrate endothelial cells

Iden, Sandra; Rehder, Daniela; August, Benjamin K.; Suzuki, Atsushi; Wolburg‐Buchholz, Karen; Wolburg, Hartwig; Ohno, Shigeo; Behrens, Jürgen; Vestweber, Dietmar; Ebnet, Klaus

doi:10.1038/sj.embor.7400819

Cited by 87 publications

(92 citation statements)

References 18 publications

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“…Genetic analysis using Drosophila embryos showed that the Drosophila homolog of Par3 (Bazooka) could establish apical complexes in the absence of AJs, indicating that Bazooka acts upstream of AJ formation (Harris and Peifer 2005). Some reports, on the other hand, suggest the AJs have a physical interaction with these polarity factors: Par3 and Par6, but not aPKC, coprecipitate with VE-cadherin, the endothelial-specific cadherin (Iden et al 2006). Par3/Bazooka colocalizes with cadherins in epithelial junctions (Harris and Peifer 2005;Afonso and Henrique 2006).…”

Section: Interactions With Cell Polarity Regulatorsmentioning

confidence: 99%

Adherens Junction: Molecular Architecture and Regulation

Meng¹,

Takeichi²

2009

Cold Spring Harbor Perspectives in Biology

509

449

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Section: Interactions With Cell Polarity Regulatorsmentioning

confidence: 99%

Adherens Junction: Molecular Architecture and Regulation

Meng¹,

Takeichi²

2009

Cold Spring Harbor Perspectives in Biology

509

449

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“…It has also been shown that upon loss of one CCM complex component, VE-cadherin and other AJ factors do not correctly localize to the basolateral side of the endothelial membrane but, instead, are diffusely localized on the cell membrane (Lampugnani et al, 2010). Under resting conditions, VE-cadherin interacts and colocalizes with members of the Par polarity complex (consisting of PAR3, PAR6 and protein kinase Cf, PKCf) (Iden et al, 2006;Lampugnani et al, 2010) and is required for the activation of PKCf. Dismantling AJs by inactivation of CCM1 leads to the abrogation of endothelial polarity, which might explain why CCMmediated lesions are abnormally enlarged and present multiple lumens.…”

Section: Mechanisms Of Induction or Inhibition Of Endothelial Permeabmentioning

confidence: 99%

Endothelial adherens junctions at a glance

Dejana

Orsenigo

2013

Journal of Cell Science

175

142

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Adherens junctions have an important role in the control of vascular permeability. These structures are located at cell-to-cell contacts, mediate cell adhesion and transfer intracellular signals. Adhesion is mediated by cadherins, which interact homophilically in trans and form lateral interactions in cis. VE-cadherin (also known as CDH5 and CD144) is the major component of endothelial adherens junctions and is specific to endothelial cells. Endothelial cells from different types of vessels, such as lymphatic vessels, arteries and veins, show differences in junction composition and organization. Vascular permeability is increased by modifications in the expression and function of adherens junction components. In some cases these defects might be cause of pathology. In this Cell Science at a Glance article, we present the example of the so-called cerebral cavernous malformation (CCM), where adherens junctions are dismantled in the vessels contributing to brain microcirculation. This causes the loss of endothelial cell apical–basal polarity and the formation of cavernomas, which are fragile and hemorrhagic. Other diseases are accompanied by persistent alterations of vascular morphology and permeability, such as seen in tumors. It will be important to achieve a better understanding of the relationship between vascular fragility, malformations and junctional integrity in order to develop more effective therapies.

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“…Consistent with this data, impaired lumen formation has been reported in zebrafish upon knockdown of expression of the gene encoding VEC (MonteroBalaguer et al, 2009). VEC can directly bind Par3, which is an element of the polarity complex (Iden et al, 2006), and it is required for junctional organization of Tiam (Lampugnani et al, 2002); however, the actual pathway through which VEC regulates endothelial polarity remains unclear.…”

Section: Introductionmentioning

confidence: 99%

CCM1 regulates vascular-lumen organization by inducing endothelial polarity

Lampugnani

Orsenigo

Rudini

et al. 2010

Journal of Cell Science

166

189

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SummaryLittle is known about the molecular mechanisms that regulate the organization of vascular lumen. In this paper we show that lumen formation correlates with endothelial polarization. Adherens junctions (AJs) and VE-cadherin (VEC, encoded by CDH5) are required for endothelial apicobasal polarity in vitro and during embryonic development. Silencing of CDH5 gene expression leads to abrogation of endothelial polarity accompanied by strong alterations in lumenal structure. VEC co-distributes with members of the Par polarity complex (Par3 and PKCz) and is needed for activation of PKCz. CCM1 is encoded by the CCM1 gene, which is mutated in 60% of patients affected by cerebral cavernous malformation (CCM). The protein interacts with VEC and directs AJ organization and AJ association with the polarity complex, both in cell-culture models and in human CCM1 lesions. Both VEC and CCM1 control Rap1 concentration at cell-cell junctions. We propose that VEC, CCM1 and Rap1 form a signaling complex. In the absence of any of these proteins, AJs are dismantled, cell polarity is lost and vascular lumenal structure is severely altered.

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A distinct PAR complex associates physically with VE‐cadherin in vertebrate endothelial cells

Cited by 87 publications

References 18 publications

Adherens Junction: Molecular Architecture and Regulation

Adherens Junction: Molecular Architecture and Regulation

Endothelial adherens junctions at a glance

CCM1 regulates vascular-lumen organization by inducing endothelial polarity

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