The endoplasmic reticulum and neuronal calcium signalling

Abstract

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.