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Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
Linking NAADP to ion channel activity: a unifying hypothesis
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
Science Signaling
|April 27, 2012
Summary
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a calcium-releasing messenger. New findings suggest specific proteins, not two-pore channels, act as the NAADP receptor, potentially explaining its regulation of various ion channels.
Area of Science:
- Cellular signaling and ion channel regulation.
- Biochemistry of second messengers.
- Molecular mechanisms of calcium release.
Background:
- Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent calcium (Ca2+)-releasing second messenger.
- NAADP is known to regulate various ion channels, including ryanodine receptors, two-pore channels, and TRP-ML1.
- The precise molecular identity of the NAADP receptor has remained elusive.
Purpose of the Study:
- To identify the molecular receptor for NAADP.
- To investigate the relationship between NAADP and two-pore channels.
- To elucidate the mechanism by which NAADP regulates diverse ion channels.
Main Methods:
- Protein labeling to identify NAADP binding proteins.
- Experimental manipulation (overexpression and knockout) of two-pore channels.
- Analysis of NAADP binding in relation to ion channel expression levels.
Main Results:
- A 22- and 23-kilodalton protein pair was identified as potential NAADP binding proteins.
- NAADP binding to these proteins was independent of two-pore channel manipulation.
- Two-pore channels are regulated by NAADP but are not the direct NAADP receptors.
Conclusions:
- The identified 22- and 23-kilodalton proteins are proposed as the receptors for NAADP.
- These NAADP binding proteins may interact with multiple ion channels, explaining NAADP's broad regulatory role.
- This finding provides a new framework for understanding NAADP-mediated calcium signaling.
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