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The endo-lysosomal system as an NAADP-sensitive acidic Ca(2+) store: role for the two-pore channels |
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| Authors: | Patel Sandip Ramakrishnan Latha Rahman Taufiq Hamdoun Amro Marchant Jonathan S Taylor Colin W Brailoiu Eugen |
| Institution: | a Department of Cell and Developmental Biology, University College London, London, UK b Department of Pharmacology, Cambridge University, Cambridge, UK c Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA d Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA e Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA |
| Abstract: | 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. |
| Keywords: | NAADP Two-pore channels TPC1 TPC2 TPCN1 TPCN2 Calcium Endosomes Lysosomes Acidic calcium stores |
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