Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content
| Autor: | Wei Ping Li, Dorothy I. Mundy, Katherine Luby-Phelps, Richard G.W. Anderson |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Endosome
Caveolin 1 Green Fluorescent Proteins CHO Cells Endosomes Biology Cell Line 03 medical and health sciences 0302 clinical medicine Cricetinae Caveolae Caveolin Animals Humans Protein Kinase Inhibitors Molecular Biology Integral membrane protein Late endosome 030304 developmental biology 0303 health sciences Mannose 6-phosphate receptor Articles Intracellular Membranes Cell Biology Hydrogen-Ion Concentration Genistein Cell biology Cytosol Cholesterol Membrane Membrane Trafficking lipids (amino acids peptides and proteins) Androstenes Lysosomes 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Caveolin-1 traffics to late endosomal/lysosomal membranes in response to manipulations of the cholesterol content of cells, suggesting that caveolin functions in the egress of cholesterol from this organelle. Cavicles associate with the periphery of the lysosome as they do with caveosomes, but these are separate organelles. 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. |
| Databáze: | OpenAIRE |
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