CCM1 regulates vascular-lumen organization by inducing endothelial polarity.

Abstract:

: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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Lampugnani MG,Orsenigo F,Rudini N,Maddaluno L,Boulday G,Chapon F,Dejana E

doi

10.1242/jcs.059329

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

1073-80

issue

Pt 7

eissn

0021-9533

issn

1477-9137

pii

123/7/1073

journal_volume

123

pub_type

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