A new VIZIB (Virtual Institute of Zinc Biology) website has been launched, with help of the Royal Society of Chemistry as part of the Zinc-net European Cooperation in Science and Technology (COST) Action chaired by Prof. Nicola Lowe (UCLAN). The purpose of the new site is for researchers interested in the study of zinc to share ideas and establish collaborations. The site can be accessed here (please note that registration is required).
The paper is out
Samantha J Pitt, Andy KM Lam, Katja Rietdorf, Antony Galione, and Rebecca Sitsapesan (2014)
Reconstituted Human TPC1 Is a Proton-Permeable Ion Channel and Is Activated by NAADP or Ca2+.
Sci Signal, 7(326):ra46.
NAADP potently triggers Ca(2+) release from acidic lysosomal and endolysosomal Ca(2+) stores. Human two-pore channels (TPC1 and TPC2), which are located on these stores, are involved in this process, but there is controversy over whether TPC1 and TPC2 constitute the Ca(2+) release channels. We therefore examined the single-channel properties of human TPC1 after reconstitution into bilayers of controlled composition. We found that TPC1 was permeable not only to Ca(2+) but also to monovalent cations and that permeability to protons was the highest (relative permeability sequence: H(+) >> K(+) > Na(+) >/= Ca(2+)). NAADP or Ca(2+) activated TPC1, and the presence of one of these ligands was required forchannel activation. The endolysosome-located lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] had no effect on TPC1 open probability but significantly increased the relative permeability of Na(+) to Ca(2+) and of H(+)to Ca(2+). Furthermore, our data showed that, although both TPC1 and TPC2 are stimulated by NAADP, these channels differ in ion selectivity and modulation by Ca(2+) and pH. We propose that NAADP triggers H(+) release from lysosomes and endolysomes through activation of TPC1, but that the Ca(2+)-releasing ability ofTPC1 will depend on the ionic composition of the acidic stores and may be influenced by other regulators that affect TPC1 ion permeation.