Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK..
Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, CNRS- University Paris-Sud, Campus CEA, 151 Rte de la Rotonde, 91400 Saclay, France..
Cell Calcium. 2022 Jun;104:102582. doi: 10.1016/j.ceca.2022.102582. Epub 2022 Apr 10.
Ca signalling is of prime importance in controlling numerous cell functions in the brain. Endolysosomes are acidic organelles currently emerging as important Ca stores in astrocytes, microglia, endothelial cells, and neurons. In neurons, these acidic Ca stores are found in axons, soma, dendrites, and axon endings and could provide local sources of Ca to control synaptic transmission, neuronal plasticity, and autophagy to name a few. This review will address how acidic Ca stores are recruited in response to cell stimulation. We will focus on the role of the endolysosomal two-pore channels (TPCs) and their physiological agonist nicotinic acid adenine dinucleotide phosphate (NAADP) and how they interact with cyclic ADP-ribose and ryanodine receptors from the endoplasmic reticulum. Finally, this review will describe new pharmacological tools and animal mutant models now available to explore acidic Ca stores as key elements in brain function and dysfunction.
钙信号在控制大脑中众多细胞功能方面至关重要。内溶酶体是目前在星形胶质细胞、小胶质细胞、内皮细胞和神经元中作为重要钙库出现的酸性细胞器。在神经元中，这些酸性钙库存在于轴突、胞体、树突和轴突末梢，可以提供局部钙源，以控制突触传递、神经元可塑性和自噬等。本综述将探讨酸性钙库如何响应细胞刺激而被募集。我们将重点关注内溶酶体双孔通道（TPCs）及其生理激动剂烟酰胺腺嘌呤二核苷酸磷酸（NAADP）的作用，以及它们如何与内质网中的环 ADP-核糖和兰尼碱受体相互作用。最后，本综述将描述现在可用于探索酸性钙库作为大脑功能和功能障碍关键因素的新药理学工具和动物突变模型。
