Endoplasmic reticulum and neuronal calcium signalling

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The endoplasmic reticulum (ER) appears as a three-dimensional network formed by an endomembrane. In neurones, the ER extends from the nucleus and the soma to the dendrites and, through the axon, to presynaptic terminals. The ER lumen is packed with enzymes that allow synthesis and post-translational folding of proteins. At the same time, the ER is involved in neuronal Ca²⁺ signalling via Ca²⁺-induced Ca²⁺ release or InsP₃-induced Ca²⁺ release, controlled by two subsets of Ca²⁺ release channels residing in the ER membrane, the ryanodine receptors (RyRs) and the InsP₃-receptors (InsP₃Rs). The ER Ca²⁺ store emerges as a single interconnected Ca²⁺ pool, although the RyRs and InsP₃Rs show heterogeneous localisation in distinct cellular sub-compartments, conferring thus specificity in local Ca²⁺ signals. The intimate mechanisms of ER integration remain largely undiscovered, yet a central role for Ca²⁺ is emerging. First, Ca²⁺ is a key input and output signal of the ER as cytosolic Ca²⁺ increases affect its concentration in the ER, and in turn, the ER Ca²⁺ release and uptake influence the cytosolic Ca²⁺ concentration. Second, the intra-ER chaperones are Ca²⁺ binding proteins, and changes in ER Ca²⁺ content affect their functional activity. Therefore, fluctuations in the ER Ca²⁺ concentration provide the link between rapid signalling and long-lasting adaptive responses. The disruption of intra-ER Ca²⁺ homeostasis can be involved in neurodegenerative disorders such as diabetic peripheral neuropathies and Alzheimer disease. [Jpn J Physiol 55 Suppl:S18 (2005)]