Caveolin-1 affects serotonin binding and cell surface levels of human 5-HT7(a) receptors.
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.
Sjögren
Benita
B
Section of Translational Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institute, 171 77 Stockholm, Sweden.
Svenningsson
Per
P
D051242:Caveolin 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D051242:Caveolin 1; D034741:RNA, Small Interfering; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D012701:Serotonin