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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 7
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pubmed:dateCreated |
2010-3-24
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pubmed:abstractText |
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 PKCzeta) and is needed for activation of PKCzeta. 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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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/KRIT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/cadherin 5,
http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1477-9137
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
123
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1073-80
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pubmed:meshHeading |
pubmed-meshheading:20332120-Adherens Junctions,
pubmed-meshheading:20332120-Animals,
pubmed-meshheading:20332120-Antigens, CD,
pubmed-meshheading:20332120-Brain Neoplasms,
pubmed-meshheading:20332120-Cadherins,
pubmed-meshheading:20332120-Cell Line,
pubmed-meshheading:20332120-Cell Polarity,
pubmed-meshheading:20332120-Endothelial Cells,
pubmed-meshheading:20332120-Genetic Predisposition to Disease,
pubmed-meshheading:20332120-Hemangioma, Cavernous, Central Nervous System,
pubmed-meshheading:20332120-Humans,
pubmed-meshheading:20332120-Mice,
pubmed-meshheading:20332120-Mice, Inbred C57BL,
pubmed-meshheading:20332120-Microtubule-Associated Proteins,
pubmed-meshheading:20332120-Multiprotein Complexes,
pubmed-meshheading:20332120-Neovascularization, Physiologic,
pubmed-meshheading:20332120-Polymorphism, Genetic,
pubmed-meshheading:20332120-Protein Binding,
pubmed-meshheading:20332120-Proto-Oncogene Proteins,
pubmed-meshheading:20332120-RNA, Small Interfering,
pubmed-meshheading:20332120-Signal Transduction,
pubmed-meshheading:20332120-rap1 GTP-Binding Proteins
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pubmed:year |
2010
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pubmed:articleTitle |
CCM1 regulates vascular-lumen organization by inducing endothelial polarity.
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pubmed:affiliation |
IFOM, FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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