Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content

Dorothy I. Mundy, Wei Ping Li, Katherine Luby-Phelps, Richard G W Anderson

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)864-880
Number of pages17
JournalMolecular Biology of the Cell
Volume23
Issue number5
DOIs
StatePublished - Mar 1 2012

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Caveolins
Caveolin 1
Endosomes
Cholesterol
Membranes
Lysosomes
Cell Membrane
Caveolae
Proton-Motive Force
Proton Pump Inhibitors
Ionophores
Cyclodextrins
Progesterone
Membrane Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content. / Mundy, Dorothy I.; Li, Wei Ping; Luby-Phelps, Katherine; Anderson, Richard G W.

In: Molecular Biology of the Cell, Vol. 23, No. 5, 01.03.2012, p. 864-880.

Research output: Contribution to journalArticle

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