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J. Biol. Chem. 277 (45): 43389-43398

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

A Molecular Sensor Detects Signal Transduction from Caveolae in Living Cells*

Masashi IsshikiDagger , Yun-shu YingDagger , Toshiro Fujita§, and Richard G. W. AndersonDagger

From the Dagger  Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039 and the § Department of Nephrology and Endocrinology, University of Tokyo, Tokyo 113-8688, Japan

Biochemical and cell fractionation studies suggest caveolae contain functionally organized sets of signaling molecules that are capable of transmitting specific signals to the cell. It is not known, however, whether any signals actually originate from caveolae in living cells. To address this question, we have engineered the calcium sensor yellow cameleon so that it is targeted either to the plasma membrane, caveolae, or the cytoplasm of endothelial cells. Quantitative measurements of the three Ca2+ pools detected by these probes indicate that caveolae are preferred sites of Ca2+ entry when Ca2+ stores in the endoplasmic reticulum are depleted. These results suggest that the signaling machinery in control of Ca2+ entry is functionally organized in the caveolae of living cells.

* This work was supported by Grants HL 20948 and GM 52016 from the National Institutes of Health, the Perot Family Foundation, the Japanese Heart Foundation Grant for Research on Hypertension and Vascular Metabolism, and the Banyu Fellowship Awards in Cardiovascular Medicine, which is sponsored by Banyu Pharmaceutical Co., Ltd., and The Merck Company Foundation.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.

To whom correspondence should be addressed: Dept. of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039. Tel.: 214-648-2346; Fax: 214-648-7577; E-mail: richard.anderson@utsouthwestern.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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