Trends in Neurosciences
ReviewCalcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders
Section snippets
ER Ca2+ signaling
Several proteins are housed in the ER that control movements of Ca2+ across its membrane under basal conditions and in response to environmental stimuli10. Under resting conditions the concentration of Ca2+ in the ER lumen is considerably higher (10–100 μm) than the Ca2+ concentration in the cytoplasm (100–300 nm). This Ca2+ gradient is maintained by an ATP-dependent pump called SERCA (smooth ER Ca2+ ATPase) in the ER membrane (Fig. 2a). ER also contains two types of Ca2+ channel, inositol
Developmental and synaptic plasticity
Roles for ER-mediated Ca2+ signaling in the regulation of neurite outgrowth and synaptogenesis are likely, but surprisingly underexplored. Studies of the expression of genes encoding IP3Rs and RyRs during development of the nervous system have established associations between different isoforms of these channels and processes such as neurite outgrowth and synaptogenesis. For example, IP31 is present in cortical neurons shortly after their migration from the ventricular zone, and its levels then
Apoptosis, excitotoxicity and neurodegenerative disorders
Apoptosis is a form of programmed cell death that normally occurs during the development of the nervous system, and can also occur in various pathological settings including Alzheimer’s, Parkinson’s and Huntington’s diseases, and stroke56, 57, 58. The biochemical cascades that lead to apoptotic cell death are being elucidated and involve activation of one or more members of a family of cysteine proteases called caspases, mitochondrial Ca2+ uptake and membrane-permeability transition, and
Conclusions and future directions
Mechanisms by which the ER controls neuronal Ca2+ homeostasis, and how this function of ER contributes to neuronal plasticity and death, are being elucidated. ER localization to dendrites, axons and their terminals (growth cones and synapses) provides for local control of Ca2+ signals that effect changes in the structure and function of neuronal circuits. Interactions of ER with Ca2+-regulating systems in the plasma membrane and mitochondria provide for complex spatial and temporal control of Ca
Acknowledgements
The authors’ research is supported by the National Institute on Aging and the Alzheimer’s Association (M.P.M.), the Medical Research Council of Canada (J.D.G. and P.N.S.), and the Alzheimer’s Society of Canada (J.D.G.).
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