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J Cell Biol. 2009 Jul 27;186(2):201-9. doi: 10.1083/jcb.200904073. Epub 2009 Jul 20.

Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling.

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  • 1Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Abstract

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a widespread and potent calcium-mobilizing messenger that is highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of the target protein is unclear. In this study, we show that the previously uncharacterized human two-pore channels (TPC1 and TPC2) are endolysosomal proteins, that NAADP-mediated calcium signals are enhanced by overexpression of TPC1 and attenuated after knockdown of TPC1, and that mutation of a single highly conserved residue within a putative pore region abrogated calcium release by NAADP. Thus, TPC1 is critical for NAADP action and is likely the long sought after target channel for NAADP.

PMID:
19620632
[PubMed - indexed for MEDLINE]
PMCID:
PMC2717647
Free PMC Article
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