Calcium Signalling: The Next Generation

Biochemical Society
9-10th October 2014

A Biochemical Society Focused Meeting

The aim of this meeting is to cover advances and controversies relating to intracellular Ca2+ channel function and dysfunction. Sessions will be led by early career scientists in order to engage “The next generation” of Ca2+ signallers. The meeting will cover contemporary developments in Ca2+ signalling mediated by the three main classes of intracellular Ca2+ release channels sensitive to NAADP, IP3 and ryanodine.


The 4th International Society for Zinc Biology Meeting

14th-19th September 2014

Zinc has important functions in initiating and regulating signal transduction as well as injury cascades in many cell systems. Zinc dyshomeostasis has been linked to several diseases, including cancer, Alzheimer’s disease, epilepsy, stroke and diabetes. Nutritional zinc deficiency, found in both developed and in third world countries, is associated with abnormal brain development and impaired learning and memory, but also with diarrhea, growth retardation and immune deficiency. The 2014 meeting will provide a detailed update by young scientists and leaders in the field of zinc biology.


VIZIB website launched

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).

Reconstituted Human TPC1 Is a Proton-Permeable Ion Channel and Is Activated by NAADP or Ca2+.

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.

Here is a link to our paper:

Crystal structure of HRG N2 domain published in Blood

We report the first structural characterisation of histidine-rich glycoprotein, an important plasma adaptor protein following elucidation of the 1.93 Å X-ray crystal structure of the protein’s N2 domain (PDB: 4CCV). This region forms part of an important ligand interaction site on the molecule, that binds a range of molecules including the natural anti-coagultant, heparin. The structure, solved in collaboration with Prof. Jim Naismith’s laboratory revealed the presence of an S-glutathionyl adduct, which has implications for the control of angiogenesis. – Open access version in Europe PMC.