Linking NAADP to ion channel activity: a unifying hypothesis
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Updated: May 22, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
1The Calcium Signalling Group, Department of Biochemistry and Signal Transduction, Centre of Experimental Medicine, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. guse@uke.de
Abstract:
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca(2+)-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 Ca(2+) 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.
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