Acidic Ca(2+) stores come to the fore

Changes in the concentration of cytosolic Ca(2+) form the basis of a ubiquitous signal transduction pathway. Accumulating evidence implicates acidic organelles in the control of Ca(2+) dynamics in organisms across phyla. In this special issue, we discuss Ca(2+) signalling by these "acidic Ca(2+) stores" which include acidocalcisomes, vacuoles, the endo-lysosomal system, lysosome-related organelles, secretory vesicles and the Golgi complex. Ca(2+) release from these morphologically very different organelles is mediated by members of the TRP channel superfamily and two-pore channels. Inositol trisphosphate and ryanodine receptors which are traditionally viewed as endoplasmic reticulum Ca(2+) release channels can also mobilize acidic Ca(2+) stores. Ca(2+) uptake into acidic Ca(2+) stores is driven by Ca(2+) ATPases and Ca(2+)/H(+) exchangers. In animal cells, the Ca(2+)-mobilizing messenger NAADP plays a central role in mediating Ca(2+) signals from acidic Ca(2+) stores through activation of two-pore channels. These signals are important for several physiological processes including muscle contraction and differentiation. Dysfunctional acidic Ca(2+) stores have been implicated in diseases such as acute pancreatitis and lysosomal storage disorders. Acidic Ca(2+) stores are therefore emerging as essential components of the Ca(2+) signalling network and merit extensive further study.