Accumulating evidence suggests that the endo-lysosomal system provides a substantial store of Ca2+ that is tapped by the Ca2+-mobilizing messenger, NAADP. In this article, we review evidence that NAADP-mediated Ca2+ release from this acidic Ca2+ store proceeds through activation of the newly described two-pore channels (TPCs). We discuss recent advances in defining the sub-cellular targeting, topology and biophysics of TPCs. We also discuss physiological roles and the evolution of this ubiquitous ion channel family.
Bibliographical noteFunding Information:
We thank Dev Churamani, Robert Hooper, Chi Li and Desmond Tobin for useful discussion, and the Bogue foundation (University College London) for facilitating staff exchange. Work in SP's laboratory is funded by the BBSRC . Work in CWT's laboratory is funded by the Wellcome Trust. TR is a Drapers’ Research Fellow at Pembroke College, Cambridge.
- Acidic calcium stores
- Two-pore channels