title: Triggering of Ca2+ signals by NAADP-gated two-pore channels: a role for membrane contact sites?
abstract: NAADP (nicotinic acid-adenine dinucleotide phosphate) is a potent Ca2+-mobilizing messenger implicated in many Ca2+-dependent cellular processes. It is highly unusual in that it appears to trigger Ca2+ release from acidic organelles such as lysosomes. These signals are often amplified by archetypal Ca2+ channels located in the endoplasmic reticulum. Recent studies have converged on the TPCs (two-pore channels) which localize to the endolysosomal system as the likely primary targets through which NAADP mediates its effects. 'Chatter' between TPCs and endoplasmic reticulum Ca2+ channels is disrupted when TPCs are directed away from the endolysosomal system. This suggests that intracellular Ca2+ release channels may be closely apposed, possibly at specific membrane contact sites between acidic organelles and the endoplasmic reticulum.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. patel.s@ucl.ac.uk
authors.forename: Sandip
authors.initials: S
authors.lastname: Patel
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D009249:NADP; C024376:NAADP