title: Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content.
abstract: Caveolin-1 is an integral membrane protein of plasma membrane caveolae. Here we report that caveolin-1 collects at the cytosolic surface of lysosomal membranes when cells are serum starved. This is due to an elevation of the intralysosomal pH, since ionophores and proton pump inhibitors that dissipate the lysosomal pH gradient also trapped caveolin-1 on late endosome/lysosomes. Accumulation is both saturable and reversible. At least a portion of the caveolin-1 goes to the plasma membrane upon reversal. Several studies suggest that caveolin-1 is involved in cholesterol transport within the cell. Strikingly, we find that blocking cholesterol export from lysosomes with progesterone or U18666A or treating cells with low concentrations of cyclodextrin also caused caveolin-1 to accumulate on late endosome/lysosomal membranes. Under these conditions, however, live-cell imaging shows cavicles actively docking with lysosomes, suggesting that these structures might be involved in delivering caveolin-1. Targeting of caveolin-1 to late endosome/lysosomes is not observed normally, and the degradation rate of caveolin-1 is not altered by any of these conditions, indicating that caveolin-1 accumulation is not a consequence of blocked degradation. We conclude that caveolin-1 normally traffics to and from the cytoplasmic surface of lysosomes during intracellular cholesterol trafficking.
authors.affiliation: Department of Internal Medicine-Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. dorothy.mundy@utsouthwestern.edu
authors.forename: Dorothy I
authors.initials: DI
authors.lastname: Mundy
authors.forename: Wei Ping
authors.initials: WP
authors.lastname: Li
authors.forename: Katherine
authors.initials: K
authors.lastname: Luby-Phelps
authors.forename: Richard G W
authors.initials: RG
authors.lastname: Anderson
mesh_terms: D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000736:Androstenes; C495540:CAV1 protein, human; D051242:Caveolin 1; D047428:Protein Kinase Inhibitors; D049452:Green Fluorescent Proteins; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D002784:Cholesterol; D019833:Genistein