An ancestral deuterostome family of two-pore channels mediates nicotinic acid adenine dinucleotide phosphate-dependent calcium release from acidic organelles. J Biol Chem 2010 Jan 29;285(5):2897-901
Date
11/27/2009Pubmed ID
19940116Pubmed Central ID
PMC2823445DOI
10.1074/jbc.C109.081943Scopus ID
2-s2.0-77449093874 (requires institutional sign-in at Scopus site) 110 CitationsAbstract
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.
Author List
Brailoiu E, Hooper R, Cai X, Brailoiu GC, Keebler MV, Dun NJ, Marchant JS, Patel SAuthor
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Calcium
Cloning, Molecular
Humans
Microscopy, Fluorescence
Molecular Sequence Data
NADP
Plasmids
Protein Isoforms
Pseudogenes
Sea Urchins
Sequence Homology, Amino Acid
