Decreased Cholesterol Impairs Cell Junctions

Science's STKE  10 Oct 2000:
Vol. 2000, Issue 53, pp. tw8
DOI: 10.1126/stke.2000.53.tw8

Endothelial cells form tight junctions and adherins junctions both in vivo and in culture. In vivo this phenomenon is essential to the proper function of the endothelial cells as a barrier between the blood vessel and the extracellular space. The formation of confluent monolayers of endothelial cells in culture is associated with increases in membrane cholesterol, increased association of annexin II with membranes, and dephosphorylation of adherins junction proteins (cadherin, β-catenin, γ-catenin, and pp120). Corvera et al. found that removal of cholesterol from confluent endothelial cells by cyclodextrin increased the tyrosine phosphorylation of pp120 and γ-catenin and disrupted adherins junctions between endothelial cells in culture. Additionally, membrane-associated annexin II was solubilized by digitonin, which selectively solubilizes cholesterol from membranes, suggesting that the association of annexin II with the membrane was dependent on the level of cholesterol. The authors suggest that cholesterol itself may be part of the regulatory pathway leading to the formation of adherins junctions.

Corvera, S., DiBonaventura, C., and Shpetner, H.S. (2000) Cell confluence-dependent remodeling of endothelial membranes mediated by cholesterol. J. Biol. Chem. 275: 31414-31421. [Abstract] [Full Text]