Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Biol. Chem. 275 (40): 31414-31421

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

Cell Confluence-dependent Remodeling of Endothelial Membranes Mediated by Cholesterol*

Silvia Corvera, Carlo DiBonaventura, , and Howard S. Shpetner{ddagger}

From the Program in Molecular Medicine and Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605

ABSTRACT Back to Top

Abstract: The plasma membranes of endothelial cells reaching confluence undergo profound structural and functional modifications, including the formation of adherens junctions, crucial for the regulation of vascular permeability and angiogenesis. Adherens junction formation is accompanied by the tyrosine dephosphorylation of adherens junctions proteins, which has been correlated with the strength and stability of adherens junctions. Here we show that cholesterol is a critical determinant of plasma membrane remodeling in cultures of growing cow pulmonary aortic endothelial cells. Membrane cholesterol increased dramatically at an early stage in the formation of confluent cow pulmonary aortic endothelial cell monolayers, prior to formation of intercellular junctions. This increase was accompanied by the redistribution of caveolin from a high density to a low density membrane compartment, previously shown to require cholesterol, and increased binding of the annexin II-p11 complex to membranes, consistent with other studies indicating cholesterol-dependent binding of annexin II to membranes. Furthermore, partial depletion of cholesterol from confluent cells with methyl-β-cyclodextrin both induced tyrosine phosphorylation of multiple membrane proteins, including adherens junctions proteins, and disrupted adherens junctions. Both effects were dramatically reduced by prior complexing of methyl-β-cyclodextrin with cholesterol. Our results reveal a novel physiological role for cholesterol regulating the formation of adherens junctions and other plasma membrane remodeling events as endothelial cells reach confluence.

Received for publication March 2, 2000. Revision received July 13, 2000.

Cell density-dependent increase in the level of protease-resistant prion protein in prion-infected Neuro2a mouse neuroblastoma cells.
S. Nakamitsu, A. Kurokawa, T. Yamasaki, M. Uryu, R. Hasebe, and M. Horiuchi (2010)
J. Gen. Virol. 91, 563-569
   Abstract »    Full Text »    PDF »
A lipid-protein hybrid model for tight junction.
D. B. N. Lee, N. Jamgotchian, S. G. Allen, M. B. Abeles, and H. J. Ward (2008)
Am J Physiol Renal Physiol 295, F1601-F1612
   Abstract »    Full Text »    PDF »
Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions.
S. Heyraud, M. Jaquinod, C. Durmort, E. Dambroise, E. Concord, J. P. Schaal, P. Huber, and D. Gulino-Debrac (2008)
Mol. Cell. Biol. 28, 1657-1668
   Abstract »    Full Text »    PDF »
Cholesterol Controls Lipid Endocytosis through Rab11.
M. Takahashi, M. Murate, M. Fukuda, S. B. Sato, A. Ohta, and T. Kobayashi (2007)
Mol. Biol. Cell 18, 2667-2677
   Abstract »    Full Text »    PDF »
Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells.
L. Song, S. Ge, and J. S. Pachter (2007)
Blood 109, 1515-1523
   Abstract »    Full Text »    PDF »
Effects of cholesterol manipulation on the signaling of the human oxytocin receptor.
A. Reversi, V. Rimoldi, S. Brambillasca, and B. Chini (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R861-R869
   Abstract »    Full Text »    PDF »
Involvement of the Annexin II-S100A10 Complex in the Formation of E-cadherin-based Adherens Junctions in Madin-Darby Canine Kidney Cells.
A. Yamada, K. Irie, T. Hirota, T. Ooshio, A. Fukuhara, and Y. Takai (2005)
J. Biol. Chem. 280, 6016-6027
   Abstract »    Full Text »    PDF »
Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport.
D. t. Vruchte, E. Lloyd-Evans, R. J. Veldman, D. C. A. Neville, R. A. Dwek, F. M. Platt, W. J. van Blitterswijk, and D. J. Sillence (2004)
J. Biol. Chem. 279, 26167-26175
   Abstract »    Full Text »    PDF »
AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane cytoarchitecture.
C. Benaud, B. J. Gentil, N. Assard, M. Court, J. Garin, C. Delphin, and J. Baudier (2004)
J. Cell Biol. 164, 133-144
   Abstract »    Full Text »    PDF »
{sigma}-1 Receptors ({sigma}1 Binding Sites) Form Raft-Like Microdomains and Target Lipid Droplets on the Endoplasmic Reticulum: Roles in Endoplasmic Reticulum Lipid Compartmentalization and Export.
T. Hayashi and T.-P. Su (2003)
J. Pharmacol. Exp. Ther. 306, 718-725
   Abstract »    Full Text »    PDF »
Regulation of the SHP-2 Tyrosine Phosphatase by a Novel Cholesterol- and Cell Confluence-dependent Mechanism.
A. Burkart, B. Samii, S. Corvera, and H. S. Shpetner (2003)
J. Biol. Chem. 278, 18360-18367
   Abstract »    Full Text »    PDF »
Rapid Nonvesicular Transport of Sterol between the Plasma Membrane Domains of Polarized Hepatic Cells.
D. Wustner, A. Herrmann, M. Hao, and F. R. Maxfield (2002)
J. Biol. Chem. 277, 30325-30336
   Abstract »    Full Text »    PDF »
Annexins: From Structure to Function.
V. Gerke and S. E. Moss (2002)
Physiol Rev 82, 331-371
   Abstract »    Full Text »    PDF »
Membrane Cholesterol, Protein Phosphorylation, and Lipid Rafts.
M. Edidin (2001)
Sci. STKE 2001, pe1
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882