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

Sjögren, Benita; Svenningsson, Per

doi:10.1016/j.febslet.2007.09.059

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Volume 581, Issue 26 , Pages 5115-5121, 30 October 2007

Caveolin-1 affects serotonin binding and cell surface levels of human 5-HT_7(a) receptors

Edited by Lukas Huber

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

Received 18 July 2007; received in revised form 23 September 2007; accepted 28 September 2007. published online 08 October 2007.

Abstract

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-β-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.