The endoplasmic reticulum and neuronal calcium signalling

The endoplasmic reticulum (ER) is a multifunctional signalling organelle regulating a wide range of neuronal functional responses. The ER is intimately involved in intracellular Ca2+ signalling, producing local or global cytosolic calcium fluctuations via Ca2+-induced Ca2+ release (CICR) or inositol-1,4,5-trisphosphate-induced Ca2+ release (IICR). The CICR and IICR are controlled by two subsets of Ca2+ release channels residing in the ER membrane, the Ca2+-gated Ca2+ release channels, generally known as ryanodine receptors (RyRs) and InsP3-gated Ca2+ release channels, referred to as InsP3-receptors (InsP3Rs). Both types of Ca2+ release channels are expressed abundantly in nerve cells and their activation triggers cytoplasmic Ca2+ signals important for synaptic transmission and plasticity. The RyRs and InsP3Rs show heterogeneous localisation in distinct cellular sub-compartments, conferring thus specificity in local Ca2+ signals. At the same time, the ER Ca2+ store emerges as a single interconnected pool fenced by the endomembrane. The continuity of the ER Ca2+ store could play an important role in various aspects of neuronal signalling. For example, Ca2+ ions may diffuse within the ER lumen with comparative ease, endowing this organelle with the capacity for “Ca2+ tunnelling”. Thus, continuous intra-ER Ca2+ highways may be very important for the rapid replenishment of parts of the pool subjected to excessive stimulation (e.g. in small compartments within dendritic spines), the facilitated removal of localised Ca2+ loads, and finally in conveying Ca2+ signals from the site of entry towards the cell interior and nucleus