Changes in cytosolic Ca2+ form the basis of a ubiquitous, evolutionary conserved signalling pathway. These Ca2+ signals drive many, if not all cellular processes from the very start of life (fertilisation), during vital processes such as neurotransmission, through to death (apoptosis). It is now clear that so-called "acidic Ca2+ stores" dynamically regulate cytosolic Ca2+ levels, both in isolation and in conjunction with the better-characterised Ca2+ stores of the endoplasmic reticulum. Acidic Ca2+ stores is an umbrella term that describes a cross-kingdom collection of morphologically distinct-yet-functionally related organelles united by their acid and Ca2+-rich interior. Lysosomes and lysosome-related organelles are key acidic Ca2+ stores that are considered functionally related to acidocalcisomes, vacuoles, endosomes, secretory granules and the Golgi complex. The Ca2+ mobilising messenger NAADP plays a critical role in controlling acidic Ca2+ store signalling.
We are i) defining the Ca2+ signalling "toolkit" (channels, transporters) of acidic Ca2+ stores at the molecular level and their evolutionary origins (form), ii) probing their physiological roles in processes such as membrane trafficking and cell migration (function) and iii) investigating how deviant signalling through these organelles can precipitate disorders such as Parkinson disease (failure).