Figure 1.

IP₃ receptors deliver Ca²⁺ to the cytosol and organelles. (A) By releasing Ca²⁺ from the endoplasmic reticulum (ER), IP₃Rs can deliver Ca²⁺ to the cytosol, to other IP₃Rs to ignite regenerative signals, or to the close appositions (membrane contact sites, supported by scaffold proteins) between the ER and other organelles. The latter include mitochondria and lysosomes, which can then accumulate Ca²⁺ via their low-affinity uptake systems from the high local Ca²⁺ concentration provided by IP₃Rs. (B) Loss of Ca²⁺ from the ER also activates STIM1, which then binds to Orai at ER–plasma membrane (PM) junctions to initiate store-operated Ca²⁺ entry (SOCE).