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.
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December 2010
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Conference Article|
November 24 2010
NAADP as an intracellular messenger regulating lysosomal calcium-release channels
Antony Galione;
Antony Galione
1
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
1To whom correspondence should be addressed (email antony.galione@pharm.ox.ac.uk).
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Anthony J. Morgan;
Anthony J. Morgan
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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Abdelilah Arredouani;
Abdelilah Arredouani
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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Lianne C. Davis;
Lianne C. Davis
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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Katja Rietdorf;
Katja Rietdorf
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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Margarida Ruas;
Margarida Ruas
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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John Parrington
John Parrington
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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Publisher: Portland Press Ltd
Received:
July 06 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (6): 1424–1431.
Article history
Received:
July 06 2010
Citation
Antony Galione, Anthony J. Morgan, Abdelilah Arredouani, Lianne C. Davis, Katja Rietdorf, Margarida Ruas, John Parrington; NAADP as an intracellular messenger regulating lysosomal calcium-release channels. Biochem Soc Trans 1 December 2010; 38 (6): 1424–1431. doi: https://doi.org/10.1042/BST0381424
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