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- Maria Grazia Lampugnani
- IFOM, FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
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- Fabrizio Orsenigo
- IFOM, FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
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- Noemi Rudini
- IFOM, FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
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- Luigi Maddaluno
- IFOM, FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
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- Gwénola Boulday
- Université de Medeciné Paris Diderot - Paris 7, 75005 Paris, France
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- Francoise Chapon
- Faculté de Mèdeciné, CHU Cote de Nacre, 14000 Caen, France
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- Elisabetta Dejana
- IFOM, FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
説明
<jats:p>Little 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 PKCζ) and is needed for activation of PKCζ. 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.</jats:p>
収録刊行物
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- Journal of Cell Science
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Journal of Cell Science 123 (7), 1073-1080, 2010-04-01
The Company of Biologists
