Yeast Cls2p/Csg2p localized on the endoplasmic reticulum membrane regulates a non-exchangeable intracellular Ca2+pool cooperatively with calcineurin

Abstract

Saccharromyces cerevisiae CLS2 gene product (Cls2p) that is localized on the endoplasmic reticulum is important for the regulation of intracellular Ca²⁺ in a compartment distinct from the vacuole. Using a vma3 mutation that impairs the Ca²⁺ sequestering activity into the vocuole, we have shown that the cls2 mutation results in 3.4-fold increase in the Ca²⁺ pool that is not exchangeable with extracellular Ca²⁺. Accumulation of Ca²⁺ within the cls2 cells is synergistically elevated by the addition of immunosuppressant, FK506. Moreover, in the vma3 background, toxicity caused by the cls2 mutation is greatly enhanced by FK506. Given that FK506 inhibits the calcineurin activity, Cls2p likely functions in releasing Ca²⁺ flux from the endoplasmic reticulum, somehow cooperating with calcineurin.