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  • NAADP
  • It is controversial whether TPC2 mediates lysosomal Ca 2+ release or selectively conducts Na + and whether the binding of nicotinic acid adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate [PI(3,5)P 2 ] is required for the activity of this ion channel. (sciencemag.org)
  • While NAADP-induced Ca 2+ -release has been found in many tissues and cell types, the molecular identity of the channel(s) conferring this release remained elusive so far. (springer.com)
  • Here, we show that TPCN2, a novel member of the two-pore cation channel family, displays the basic properties of native NAADP-dependent Ca 2+ -release channels. (springer.com)
  • In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca 2+ -release channel. (springer.com)
  • Other studies suggested that members of the transient receptor potential (TRP) channel family including TRPM2 [ 1 ] and TRPML1 [ 34 ] may be the cellular target protein of NAADP. (springer.com)
  • However, the micromolar concentrations of NAADP required to fully activate these channel are one to two orders higher than those found for NAADP-mediated Ca 2+ -release in a variety of cells. (springer.com)
  • In this thesis I have shown that NAADP-evoked Ca²⁺ release from lysosomes is underpinned by two-pore channels (TPCs), of which there are 3 subtypes, TPC1, TPC2 and TPC3. (st-andrews.ac.uk)
  • The two-pore channels (TPCs) are currently strong candidates for being key components of NAADP-regulated Ca2+ channels. (ovid.com)
  • Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal membrane. (abcam.com)
  • NAADP activates two-pore channels on T cell cytolytic granules to stimulate exocytosis and killing. (ox.ac.uk)
  • Here we identify the Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) and its recently identified molecular target, two-pore channels (TPCs), as being important for T cell receptor signaling in CTLs. (ox.ac.uk)
  • We demonstrate that cytolytic granules are not only reservoirs of cytolytic proteins but are also the acidic Ca(2+) stores mobilized by NAADP via TPC channels on the granules themselves, so that TPCs migrate to the immunological synapse upon CTL activation. (ox.ac.uk)
  • Nicotinic acid adenine dinucleotide phosphate (NAADP), generated in β-cells in response to high glucose, is a potent mobiliser of these stores, and has been proposed to act through two pore channels (TPC1 and TPC2, murine gene names Tpcn1 and Tpcn2). (ox.ac.uk)
  • permeation pathway
  • In contrast to previous models that invoked interactions between anions bound concurrently inside the pore, we propose that Pt(NO2) 4 2− and Fe(CN) 6 3− binding to an extracellularly accessible site outside of the channel permeation pathway alters the structure of an intracellular anion binding site, leading to weakened binding of intracellular blocking ions. (deepdyve.com)
  • extracellular
  • b ) Single channel trace (upper panel) and histogram (lower panel) of Na + conduction in MthK at -100 mV in the absence of K + . ( c ) Reverse potential of MthK measured with 100 mM KCl / 170 mM NaCl on the intracellular side and 10 mM KCl / 260 mM NaCl on the extracellular side. (nih.gov)
  • TPC2
  • identified mTORC1 inhibition as a mechanism for activation of the ion channel TPC2 that led to the mobilization of Ca 2+ from lysosomes. (sciencemag.org)
  • The two pore channel TPC2 is dispensable in pancreatic β-cells for normal Ca²⁺ dynamics and insulin secretion. (ox.ac.uk)
  • putative
  • Its amino acid sequence shares 25% identity with mouse TWIK-1, 22% with mouse TREK-1, and 33% with a putative K+ channel of Caenorhabditis elegans (C40C9). (ovid.com)
  • roles
  • The inward rectifier potassium (Kir) channel Kir4.1 (KCNJ10) carries out important physiological roles in epithelial cells of the kidney, astrocytes in the central nervous system, and stria vascularis of the inner ear. (aspetjournals.org)
  • interaction
  • To test for the possible through-space nature of ion-ion interactions inside the CFTR pore, we investigated the interaction between impermeant anions applied to either end of the pore. (deepdyve.com)
  • underlie
  • Nevertheless, well designed experimental strategies can reveal important information about the likely mechanisms that underlie the function of these channels. (rupress.org)
  • open probability
  • The D292N mutation also affected the limiting open probability: at 0 mV, the limiting open probability dropped from ∼0.5 for the wild-type channel to 0.06 in D292N (in 1 mM [Ca 2+ ] i ). (rupress.org)