Two-pore channels and NAADP-mediated endolysosomal Ca2+ signalling in health and disease

Calcium ions are important signalling molecules regulating a multitude of processes, from fertilisation to cell death. Different stimuli and their combinations generate specific spatiotemporal calcium signals, which are decoded into distinct cellular responses. Cracking this code requires a detailed understanding of the spatial and temporal choreography of the messengers, proteins and organelles that generate these calcium signatures. Nicotinic acid adenine dinucleotide phosphate (NAADP) is unique in evoking calcium release from acidic endolysosomes, and recent work suggests that two-pore channels (TPCs) – a novel family of endolysosomal channels – are the target calcium channels for NAADP. Professor Galione's research aims to clarify fundamental aspects of NAADP signalling, particularly mechanisms by which cellular stimuli induce changes in NAADP levels, how NAADP mobilises calcium from the endolysosomal stores (particularly the precise roles of the TPCs), and the specific roles of endolysosomal calcium stores in (patho)physiological processes.