Internal Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ in vivo. Vacuolar Ca²⁺, which is the major intracellular Ca²⁺ store in yeast, is required for this response, whereas extracellular Ca²⁺ is not. We aimed to identify the channel responsible for this regulated vacuolar Ca²⁺ release. Here we report that Yvc1p, a vacuolar membrane protein with homology to transient receptor potential (TRP) channels, mediates the hyperosmolarity induced Ca²⁺ release. After this release, low cytosolic Ca²⁺ is restored and vacuolar Ca²⁺ is replenished through the activity of Vcx1p, a Ca²⁺/H⁺ exchanger. These studies reveal a novel mechanism of internal Ca²⁺ release and establish a new function for TRP channels.