Contribution of annexin 2 to the architecture of mature endothelial adherens junctions.
The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.
Heyraud
Stéphanie
S
iRTSV, APV, INSERM U882, CEA-Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France.
Jaquinod
Michel
M
Durmort
Claire
C
Dambroise
Emilie
E
Concord
Evelyne
E
Schaal
Jean Patrick
JP
Huber
Philippe
P
Gulino-Debrac
Danielle
D
D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism*; D017302:Annexins / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D011233:Precipitin Tests; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000494:pharmacology
D017302:Annexins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015820:Cadherins; D034741:RNA, Small Interfering; D053778:Thiazolidines; D042461:Vascular Endothelial Growth Factor A; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C037068:latrunculin B