MECHANISMS OF SIGNAL TRANSDUCTION
Caveolin-1 Expression Inhibits Wnt/β-Catenin/Lef-1 Signaling by Recruiting β-Catenin to Caveolae Membrane Domains*

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Caveolin-1 is a principal component of caveolae membranes. In NIH 3T3 cells, caveolin-1 expression is dramatically up-regulated in confluent cells and localizes at areas of cell-cell contact. However, it remains unknown whether caveolin-1 is involved in cell-cell signaling. Here, we examine the potential role of caveolin-1 in regulating β-catenin signaling. β-Catenin plays a dual role in the cell, linking E-cadherin to the actin cytoskeleton and in Wnt signaling by forming a complex with members of the lymphoid enhancing factor (Lef-1) family of transcription factors. We show that E-cadherin, β-catenin, and γ-catenin (plakoglobin) are all concentrated in caveolae membranes. Moreover, we demonstrate that activation of β-catenin/Lef-1 signaling by Wnt-1 or by overexpression of β-catenin itself is inhibited by caveolin-1 expression. We also show that recombinant expression of caveolin-1 in caveolin-1 negative cells is sufficient to recruit β-catenin to caveolae membranes, thereby blocking β-catenin-mediated transactivation. These results suggest that caveolin-1 expression can modulate Wnt/β-catenin/Lef-1 signaling by regulating the intracellular localization of β-catenin.

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Published, JBC Papers in Press, May 17, 2000, DOI 10.1074/jbc.M002020200

*

This work was supported by grants from the National Institutes of Health, the G. Harold and Leila Y. Mathers Foundation, the Culpeper Foundation, the Kimmel Foundation, the Muscular Dystrophy Association, and the Komen Breast Cancer Foundation (to M.P.L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

FNe

Supported by National Institutes of Health Grant R01-GM-5576001, The International Spinal Research Trust Grant STR-022, and The National Multiple Sclerosis Society Grant RG-2785B3.

FNg

The incumbent of the Lunenfeld-Kunin Chair in Cell Biology and Genetics.

i

Supported in part by National Institutes of Health Grants R01-CA-70897, R01-CA-75503, and P50-HL-56399. Recipient of the Irma T. Hirschl award and an award from the Susan G. Komen Breast Cancer Foundation.

FNk

Supported by National Institutes of Health Grant R01-CA47207 and by an Irma T. Hirschl Career Scientist Award.