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 PKC zeta) and is needed for activation of PKC zeta. 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.

CCM1 regulates vascular-lumen organization by inducing endothelial polarity / M.G. Lampugnani, F. Orsenigo, N. Rudini, L. Maddaluno, G. Boulday, F. Chapon, E. Dejana. - In: JOURNAL OF CELL SCIENCE. - ISSN 0021-9533. - 123:7(2010), pp. 1073-1080. [10.1242/jcs.059329]

CCM1 regulates vascular-lumen organization by inducing endothelial polarity

N. Rudini;L. Maddaluno;E. Dejana
Ultimo
2010

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 PKC zeta) and is needed for activation of PKC zeta. 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.
Adherens junctions ; Cell polarity ; Endothelium ; Vascular lumen
Settore MED/04 - Patologia Generale
2010
Article (author)
File in questo prodotto:
File Dimensione Formato  
1073.full.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 3.09 MB
Formato Adobe PDF
3.09 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/141563
Citazioni
  • ???jsp.display-item.citation.pmc??? 95
  • Scopus 144
  • ???jsp.display-item.citation.isi??? 147
social impact