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

Eugen Brailoiu, Dev Churamani, Xinjiang Cai, Michael G. Schrlau, G. Cristina Brailoiu, Xin Gao, Robert Hooper, Michael J. Boulware, Nae J. Dun, Jonathan S. Marchant, Sandip Patel

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)201-209
Number of pages9
JournalJournal of Cell Biology
Volume186
Issue number2
DOIs
StatePublished - Jul 27 2009

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