Spatial-temporal patterning of Ca²⁺ signals by the subcellular distribution of IP₃ and IP₃ receptors

The patterning of cytosolic Ca²⁺ signals in space and time underlies their ubiquitous ability to specifically regulate numerous cellular processes. Signals mediated by liberation of Ca²⁺ sequestered in the endoplasmic reticulum (ER) through inositol trisphosphate receptor (IP₃R) channels constitute a hierarchy of events; ranging from openings of individual IP₃ channels, through the concerted openings of several clustered IP₃Rs to generate local Ca²⁺ puffs, to global Ca²⁺ waves and oscillations that engulf the entire cell. Here, we review recent progress in elucidating how this hierarchy is shaped by an interplay between the functional gating properties of IP₃Rs and their spatial distribution within the cell. We focus in particular on the subset of IP₃Rs that are organized in stationary clusters and are endowed with the ability to preferentially liberate Ca²⁺.