Linking NAADP to Ion Channel Activity: A Unifying Hypothesis

Sci. Signal., 24 April 2012
Vol. 5, Issue 221, p. pe18
DOI: 10.1126/scisignal.2002890

Linking NAADP to Ion Channel Activity: A Unifying Hypothesis

  1. Andreas H. Guse*
  1. The Calcium Signalling Group, Department of Biochemistry and Signal Transduction and Department of Biochemistry and Molecular Cell Biology, Centre of Experimental Medicine, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
  1. *Corresponding author. Telephone, 49-40-74105-2828; fax, 49-40-74105-6818; e-mail, guse{at}


Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-releasing second messenger that might regulate different ion channels, including the ryanodine receptor, two-pore channels, and TRP-ML1 (transient receptor potential channel, subtype mucolipin 1), a Ca2+ channel localized to lysosomes. New evidence suggests that a 22- and 23-kilodalton pair of proteins could be the receptor for NAADP. Labeling of NAADP binding proteins was independent of overexpression or knockout of two-pore channels, indicating that two-pore channels, although regulated by NAADP, are not the NAADP receptors. I propose that NAADP binding proteins could bind to different ion channels and thus may explain how NAADP regulates diverse ion channels.


A. H. Guse, Linking NAADP to Ion Channel Activity: A Unifying Hypothesis. Sci. Signal. 5, pe18 (2012).

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