Internal Ca(2+) release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue.
Calcium ions, present inside all eukaryotic cells, are important second messengers in the transduction of biological signals. In mammalian cells, the release of Ca(2+) from intracellular compartments is required for signaling and involves the regulated opening of ryanodine and inositol-1,4,5-trisphosphate (IP3) receptors. However, in budding yeast, no signaling pathway has been shown to involve Ca(2+) release from internal stores, and no homologues of ryanodine or IP3 receptors exist in the genome. Here we show that hyperosmotic shock provokes a transient increase in cytosolic Ca(2+) in vivo. Vacuolar Ca(2+), which is the major intracellular Ca(2+) store in yeast, is required for this response, whereas extracellular Ca(2+) is not. We aimed to identify the channel responsible for this regulated vacuolar Ca(2+) release. Here we report that Yvc1p, a vacuolar membrane protein with homology to transient receptor potential (TRP) channels, mediates the hyperosmolarity induced Ca(2+) release. After this release, low cytosolic Ca(2+) is restored and vacuolar Ca(2+) is replenished through the activity of Vcx1p, a Ca(2+)/H(+) exchanger. These studies reveal a novel mechanism of internal Ca(2+) release and establish a new function for TRP channels.
Denis
Valerie
V
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Cyert
Martha S
MS
D000331:Aequorin; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006982:Hypertonic Solutions / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009997:Osmotic Pressure / Q000187:drug effects; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D050052:TRPC Cation Channels; D014617:Vacuoles / Q000378:metabolism
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D006982:Hypertonic Solutions; D029701:Saccharomyces cerevisiae Proteins; D050052:TRPC Cation Channels; C446509:Yvc1 protein, S cerevisiae; D000331:Aequorin; D002122:Calcium Chloride; D002118:Calcium