Flotillin-1 stabilizes caveolin-1 in intestinal epithelial cells.
Flotillins and caveolins represent two types of resident proteins associated with lipid rafts in mammalian cells, however, their possible cross-talk in regulating lipid raft functions remains poorly understood. In this report, we observed that siRNA-mediated down-regulation of flotillin-1 expression which disrupted lipid raft-mediated endocytosis of BODIPY FL C(5)-lactosylceramide also substantially decreased caveolin-1 level in SK-CO15 human intestinal epithelial cells. The decrease in caveolin-1 expression appeared to be specific for flotillin-1 knock-down and was not observed after down-regulation of flotillin-2. The decrease in caveolin-1 level in flotillin-1-depleted cells was not due to suppression of its mRNA synthesis and was not mimicked by cholesterol depletion of SK-CO15 cells. Furthermore, flotillin-1 dependent down-regulation of caveolin-1 was reversed after cell exposure to lysosomal inhibitor, chloroquine but not proteosomal inhibitor, MG262. Our data suggest that flotillin-1 regulates caveolin-1 level by preventing its lysosomal degradation in intestinal epithelial cells.
Vassilieva
Elena V
EV
Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Whitehead Research Building, 615 Michael Street, Atlanta, Georgia 30322, USA.
Ivanov
Andrei I
AI
Nusrat
Asma
A
D001896:Boron Compounds / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007790:Lactosylceramides / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*
C527196:BODIPY-LacCer; D001896:Boron Compounds; D051242:Caveolin 1; D007790:Lactosylceramides; D008565:Membrane Proteins; C106354:flotillins