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+