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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 PMID: 19940116 PMCID: PMC2823445


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 S


Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Cloning, Molecular
Microscopy, Fluorescence
Molecular Sequence Data
Protein Isoforms
Sea Urchins
Sequence Homology, Amino Acid

View this publication's entry at the Pubmed website PMID: 19940116
jenkins-FCD Prod-130 96200611f8481f0aa4f84230b11dd74d063847a3