title: An ancestral deuterostome family of two-pore channels mediates nicotinic acid adenine dinucleotide phosphate-dependent calcium release from acidic organelles.
abstract: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent and widespread calcium-mobilizing messenger, the properties of which have been most extensively described in sea urchin eggs. The molecular basis for calcium release by NAADP, however, is not clear and subject to controversy. Recent studies have provided evidence that members of the two-pore channel (TPC) family in mammals are the long sought after target channels for NAADP. Here, we show that the TPC3 gene, which has yet to be functionally characterized, is present throughout the deuterostome lineage but is a pseudogene in humans and other primates. We report the molecular cloning of the complete ancestral TPC gene family from the sea urchin and demonstrate that all three isoforms localize to acidic organelles to mediate NAADP-dependent calcium release. Our data highlight the functional divergence of this novel gene family during deuterostome evolution and provide further evidence that NAADP mediates calcium release from acidic stores through activation of TPCs.
authors: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors: Eugen
authors: E
authors: Brailoiu
authors: Robert
authors: R
authors: Hooper
authors: Xinjiang
authors: X
authors: Cai
authors: G Cristina
authors: GC
authors: Brailoiu
authors: Michael V
authors: MV
authors: Keebler
authors: Nae J
authors: NJ
authors: Dun
authors: Jonathan S
authors: JS
authors: Marchant
authors: Sandip
authors: S
authors: Patel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D008969:Molecular Sequence Data; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms; D011544:Pseudogenes; D012617:Sea Urchins; D017386:Sequence Homology, Amino Acid
chemical_list: D020033:Protein Isoforms; D009249:NADP; C024376:NAADP; D002118:Calcium