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Department of Pharmacology

 
Author(s): 
Brailoiu, E, Rahman, T, Churamani, D, Prole, DL, Brailoiu, GC, Hooper, R, Taylor, CW, Patel, S
Abstract: 

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous messenger proposed to stimulate Ca(2+) release from acidic organelles via two-pore channels (TPCs). It has been difficult to resolve this trigger event from its amplification via endoplasmic reticulum Ca(2+) stores, fuelling speculation that archetypal intracellular Ca(2+) channels are the primary targets of NAADP. Here, we redirect TPC2 from lysosomes to the plasma membrane and show that NAADP evokes Ca(2+) influx independent of ryanodine receptors and that it activates a Ca(2+)-permeable channel whose conductance is reduced by mutation of a residue within a putative pore. We therefore uncouple TPC2 from amplification pathways and prove that it is a pore-forming subunit of an NAADP-gated Ca(2+) channel.

Publication ID: 
200579
Published date: 
3 December 2010
Publication source: 
pubmed
Publication type: 
Journal articles
Journal name: 
J Biol Chem
Publication volume: 
285
Publisher: 
Parent title: 
Edition: 
Publication number: