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ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling
- Source :
- Cell Communication and Signaling, Cell Communication and Signaling, BioMed Central, 2014, 12 (1), pp.12. ⟨10.1186/1478-811X-12-12⟩, Cell Communication and Signaling : CCS
- Publication Year :
- 2014
- Publisher :
- Springer Verlag, 2014.
-
Abstract
- Background Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis. Results In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ΔERM) or the cytoplasmic tail (IC2 ΔTAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls. Conclusions These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.
- Subjects :
- rac1 GTP-Binding Protein
Angiogenesis
Vascular permeability
Biochemistry
Mice
CYTOPLASMIC DOMAIN
[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Cell adhesion molecule
Microfilament Proteins
Ce ll adhesion
Gap Junctions
Intercellular adhesion molecule
Cadherins
Cell-cell junctions
Cell biology
Rac-1
Protein Transport
ERM
Life Sciences & Biomedicine
Protein Binding
Signal Transduction
Biochemistry & Molecular Biology
ICAM-2
VE-CADHERIN
Biology
Permeability
ADHESION MOLECULES
TUMOR ANGIOGENESIS
Cell-cell junction
Endothelial
Adherens junction
HUMAN ENDOTHELIAL-CELLS
Capillary Permeability
RHO
Antigens, CD
Cell Line, Tumor
Human Umbilical Vein Endothelial Cells
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Cell adhesion
Molecular Biology
ADHERENS JUNCTION
N-Cadherin
0604 Genetics
Science & Technology
Binding Sites
Cadherin
Research
Contact inhibition
0601 Biochemistry And Cell Biology
Membrane Proteins
IN-VITRO
Cell Biology
Cytoskeletal Proteins
GTPASES
Cell Adhesion Molecules
Subjects
Details
- Language :
- English
- ISSN :
- 1478811X
- Database :
- OpenAIRE
- Journal :
- Cell Communication and Signaling, Cell Communication and Signaling, BioMed Central, 2014, 12 (1), pp.12. ⟨10.1186/1478-811X-12-12⟩, Cell Communication and Signaling : CCS
- Accession number :
- edsair.doi.dedup.....73ed9e0744a2d3f641bd2483cd023667