Recent studies into the mechanisms of action of the Ca2+-mobilizing messenger NAADP (nicotinic acid–adenine dinucleotide phosphate) have demonstrated that a novel family of intracellular Ca2+-release channels termed TPCs (two-pore channels) are components of the NAADP receptor. TPCs appear to be exclusively localized to the endolysosomal system. These findings confirm previous pharmacological and biochemical studies suggesting that NAADP targets acidic Ca2+ stores rather than the endoplasmic reticulum, the major site of action of the other two principal Ca2+-mobilizing messengers, InsP3 and cADPR (cADP-ribose). Studies of the messenger roles of NAADP and the function of TPCs highlight the novel role of lysosomes and other organelles of the endocytic pathway as messenger-regulated Ca2+ stores which also affects the regulation of the endolysosomal system.
- calcium-release channel
- endolysosomal system
- nicotinic acid–adenine dinucleotide phosphate (NAADP)
- two-pore channel (TPC)
Lysosomes in Health and Disease: A Biochemical Society Focused Meeting held at Charles Darwin House, London, U.K., 13–14 May 2010. Organized and Edited by Frances Platt (Oxford, U.K.) and Paul Pryor (York, U.K.).
Abbreviations: cADPR, cADP-ribose; CICR, Ca2+-induced Ca2+ release; ER, endoplasmic reticulum; GPN, glycylphenylalanine 2-naphthylamide; HEK, human embryonic kidney; IP3R, InsP3 receptor; LAMP, lysosome-associated membrane protein; NAADP, nicotinic acid–adenine dinucleotide phosphate; RyR, ryanodine receptor; TPC, two-pore channel; AtTPC1, Arabidopsis thaliana TPC1; TRP, transient receptor potential; TRPM2, TRP melastatin 2
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