Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. J Cell Biol 2009 Jul 27;186(2):201-9
Date
07/22/2009Pubmed ID
19620632Pubmed Central ID
PMC2717647DOI
10.1083/jcb.200904073Scopus ID
2-s2.0-67749143745 (requires institutional sign-in at Scopus site) 354 CitationsAbstract
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.
Author List
Brailoiu E, Churamani D, Cai X, Schrlau MG, Brailoiu GC, Gao X, Hooper R, Boulware MJ, 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 Channels
Calcium Signaling
Cells, Cultured
Endosomes
Humans
Lysosomes
Molecular Sequence Data
Mutation
NADP
Phylogeny
Sequence Alignment
