Caveolin-1 alters the pattern of cytoplasmic Ca2+ oscillations and Ca2+-dependent gene expression by enhancing leukotriene receptor desensitization.
Bottom Line: Here, we show that the scaffolding protein caveolin-1 has a profound effect on receptor-driven Ca(2+) signals and downstream gene expression.Mutagenesis studies revealed that these effects required a functional scaffolding domain within caveolin-1.Our results reveal that caveolin-1 is a bimodal regulator of receptor-dependent Ca(2+) signaling, which fine-tunes the spatial and temporal profile of the Ca(2+) rise and thereby its ability to activate the NFAT pathway.
Affiliation: From the Department of Physiology, Anatomy, and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom and.Show MeSH
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Mentions: Endogenous levels of caveolin-1 were virtually undetectable in Western blots from RBL-1 cells (data not shown), so we overexpressed the GFP-tagged protein to study its impact on Ca2+ oscillations. In non-transfected (wild type) cells, stimulation with LTC4 evoked a series of cytoplasmic Ca2+ oscillations (Fig. 1A), which decreased slightly over time due to receptor desensitization (Fig. 1B) (6). Expression of caveolin-1-GFP substantially altered the pattern of the Ca2+ oscillations (Fig. 1A, dotted trace). The amplitudes of the initial Ca2+ oscillations evoked by LTC4 were now considerably larger than in non-transfected cells (Fig. 1, A and C), but the oscillations ran down more quickly and so were fewer in number over a 600 to 700-s recording period (Fig. 1B). Analysis of the various oscillatory parameters revealed that the total Ca2+ rise associated with each oscillation (area under the spike) was significantly larger in cells expressing caveolin-1-GFP (Fig. 1D); this reflected both an increase in the amplitude of each Ca2+ oscillation (Fig. 1C) as well as an increase in duration (Fig. 1E). Cytoplasmic Ca2+ during each oscillation was therefore elevated for a longer time in the presence of caveolin-1-GFP.
Affiliation: From the Department of Physiology, Anatomy, and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom and.