title: Function and dysfunction of two-pore channels.
abstract: Two-pore channels (TPCs) are evolutionarily important members of the voltage-gated ion channel superfamily. TPCs localize to acidic Ca(2+) stores within the endolysosomal system. Most evidence indicate that TPCs mediate Ca(2+) signals through the Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) to control a range of Ca(2+)-dependent events. Recent studies clarify the mechanism of TPC activation and identify roles for TPCs in disease, highlighting the regulation of endolysosomal membrane traffic by local Ca(2+) fluxes. Chemical targeting of TPCs to maintain endolysosomal "well-being" may be beneficial in disorders as diverse as Parkinson's disease, fatty liver disease, and Ebola virus infection.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. E-mail: patel.s@ucl.ac.uk.
authors.forename: Sandip
authors.initials: S
authors.lastname: Patel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008954:Models, Biological; D009249:NADP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000097903:Two-Pore Channels
chemical_list: D002118:Calcium; D015220:Calcium Channels; D009249:NADP; C407357:TPCN1 protein, human; D000097903:Two-Pore Channels; C530224:TPCN2 protein, human; C024376:NAADP