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Review
. 2021 Sep 7:12:703326.
doi: 10.3389/fimmu.2021.703326. eCollection 2021.

NAADP: From Discovery to Mechanism

Timothy F Walseth  1 , Andreas H Guse  2
Affiliations
Review

NAADP: From Discovery to Mechanism

Timothy F Walseth et al. Front Immunol. .

Abstract

Nicotinic acid adenine dinucleotide 2'-phosphate (NAADP) is a naturally occurring nucleotide that has been shown to be involved in the release of Ca2+ from intracellular stores in a wide variety of cell types, tissues and organisms. Current evidence suggests that NAADP may function as a trigger to initiate a Ca2+ signal that is then amplified by other Ca2+ release mechanisms. A fundamental question that remains unanswered is the identity of the NAADP receptor. Our recent studies have identified HN1L/JPT2 as a high affinity NAADP binding protein that is essential for the modulation of Ca2+ channels.

Keywords: HN1L/JPT2; NAADP; calcium signaling; ryanodine receptor; two-pore channel.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
HN1L/JPT2 co-localization with ryanodine receptors and scheme of Ca2+ microdomain formation by ryanodine receptors and ORAI1 channels in ER-PM junctions of T cells. Left: Co-localization of HN1L/JPT2 with RYR shown by super-resolution microscopy in a single Jurkat T cell [image taken from Figure 6 of (45)]. From (52). Reprinted with permission from AAAS. Right: scheme of Ca2+ microdomain formation by RYRs and ORAI1 channels in ER-PM junctions of T cells. Abbreviations used: STIM1/2, stromal interaction molecule 1 and/or 2.
Figure 2
Figure 2
HNL1/JPT2 interacts with TPC1 and is essential for NAADP-evoked calcium signaling via two pore channels.
See this image and copyright information in PMC

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