Release and uptake mechanisms of vesicular Ca²⁺ stores

Cells utilize calcium ions (Ca²⁺) to signal almost all aspects of cellular life, ranging from cell proliferation to cell death, in a spatially and temporally regulated manner. A key aspect of this regulation is the compartmentalization of Ca²⁺ in various cytoplasmic organelles that act as intracellular Ca²⁺ stores. Whereas Ca²⁺ release from the large-volume Ca²⁺ stores, such as the endoplasmic reticulum (ER) and Golgi apparatus, are preferred for signal transduction, Ca²⁺ release from the small-volume individual vesicular stores that are dispersed throughout the cell, such as lysosomes, may be more useful in local regulation, such as membrane fusion and individualized vesicular movements. Conceivably, these two types of Ca²⁺ stores may be established, maintained or refilled via distinct mechanisms. ER stores are refilled through sustained Ca²⁺ influx at ER-plasma membrane (PM) membrane contact sites (MCSs). In this review, we discuss the release and refilling mechanisms of intracellular small vesicular Ca²⁺ stores, with a special focus on lysosomes. Recent imaging studies of Ca²⁺ release and organelle MCSs suggest that Ca²⁺ exchange may occur between two types of stores, such that the small stores acquire Ca²⁺ from the large stores via ER-vesicle MCSs. Hence vesicular stores like lysosomes may be viewed as secondary Ca²⁺ stores in the cell.