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FEBS Lett. 2007 Oct 30;581(26):5115-21. Epub 2007 Oct 8.

Caveolin-1 affects serotonin binding and cell surface levels of human 5-HT7(a) receptors.

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Section of Translational Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institute, 171 77 Stockholm, Sweden.


Studies using HeLa cells expressing 5-HT7 receptors showed that detergent resistant membranous lipid rafts purified by sucrose gradient centrifugation contained 5-HT7 receptors and caveolin-1. Caveolin-1 siRNA-mediated knockdown or serotonin (5-HT) treatment caused significant reductions of maximum [3H]5-HT binding to 5-HT7 receptors and total immunoreactivity of membranous 5-HT7 receptors in intact cells. Co-treatment with 5-HT, caveolin-1 siRNA and methyl-beta-cyclodextrin had no additive effects on reducing maximum binding of [3H]5-HT to 5-HT7 receptors. 5-HT-mediated reduction of [3H]5-HT binding to 5-HT7 receptors was counteracted by genistein, but not by sucrose. Caveolin-1, specifically localized in cholesterol-enriched lipid rafts, appears to regulate constitutive and agonist-stimulated cell surface levels of 5-HT7 receptors via a clathrin-independent mechanism.

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