The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca2+ release channels

摘要

In this review, we describe the background and implications of our recent discovery that two-pore channels (TPCs) comprise a novel class of calcium release channels gated by the intracellular messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Their localisation to the endolysosomal system highlights a new function for these organelles as targets for NAADP-mediated Ca2+ mobilisation. In addition, we describe how TPCs may also trigger further Ca2+ release by coupling to the endoplasmic reticular stores through activation of IP₃ receptors and ryanodine receptors. Keywords Inositol 1,4,5-trisphosphate - Pancreatic β-cell - Endothelin - Cholecystokinin - Ca2+-induced Ca2+ release - Ion channel - Ca2+ mobilisation - Ca2+ stores - Calcium signalling - Calcium transient