title: The Molecular Basis for Ca2+Signalling by NAADP: Two-Pore Channels in a Complex?
abstract: NAADP is a potent Ca2+mobilizing messenger in a variety of cells but its molecular mechanism of action is incompletely understood. Accumulating evidence indicates that the poorly characterized two-pore channels (TPCs) in animals are NAADP sensitive Ca2+-permeable channels. TPCs localize to the endo-lysosomal system but are functionally coupled to the better characterized endoplasmic reticulum Ca2+channels to generate physiologically relevant complex Ca2+signals. Whether TPCs directly bind NAADP is not clear. Here we discuss the idea based on recent studies that TPCs are the pore-forming subunits of a protein complex that includes tightly associated, low molecular weight NAADP-binding proteins.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, MN 55455, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Marchant
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, MN 55455, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Lin-Moshier
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, MN 55455, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Walseth
authors.affiliation: Department of Cell and Developmental Biology, University College London, WC1E 6BT, UK.
authors.forename: Sandip
authors.initials: S
authors.lastname: Patel
keywords: Ca2+ Signaling; Endosomes; Lysosomes; NAADP; Photoaffinity Labelling; Two-Pore Channels