Calcium signalling by nicotinic acid adenine dinucleotide phosphate (NAADP)

Abstract

Intracellular Ca2+ signals are coordinated to elicit spatiotemporal patterns. These include repetitive Ca 2+ transients, which may be localized or propagated as regenerative waves that may also pass into neighbouring cells [1][2][3]. d-myo-Inositol 1,4,5-trisphosphate (InsP 3 ) is a well-established intracellular Ca 2+ mobilizing messenger in many cell types [3], and is a paradigm for additional molecules that release Ca 2+ from intracellular Ca 2+ stores. Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) were first discovered in the sea urchin egg as novel Ca 2+ mobilizing agents [4][5][6]. In this cell, cADPR was shown to target ryanodine receptors (RyRs) to release Ca 2+ from the endoplasmic reticulum (ER), and now has been established as an intracellular messenger in several cell types [7,8]. In contrast, NAADP was found to activate a Ca 2+ release mechanism distinct from those activated by InsP 3 and cADPR, based on pharmacology and self-induced inactivation of the different Ca 2+ release mechanisms. It has thus been of great interest to investigate the physiology, enzymology and pharmacology of the NAADP signalling pathway. Recent reports have shown increases in NAADP levels in response to cellular stimuli fulfilling a major criterion for the classification of NAADP as a second messenger not only in sea urchin eggs but also in mammalian cells [9][10][11][12]. Here we focus on the Ca 2+ mobilizing properties of NAADP and compare them with the actions of InsP 3 and cADPR. Distinct properties of NAADPSince the discovery of NAADP as a Ca 2+ mobilizing molecule in sea urchin egg homogenates, the sea urchin egg has remained an important system in which to study the actions of NAADP. NAADP has an ability to release Ca 2+ from intracellular Ca 2+ stores and is the most potent Ca 2+ mobilizing agent described so [14,21,29]. Therefore in contrast to [43]. A second model, the two pool or trigger hypothesis, is based on the idea that there is a distinct NAADP-sensitive storage organelle, possibly an thapsigargin-insensitive acidic store [28], that is responsible for a localized signal which is amplified by InsP 3 Rs and RyRs the on the ER by CICR [22,34,36,38]. This model accounts for the finding in some cells that localized NAADP-induced signals persist in the presence of InsP 3 Rs and RyR antagonists or thapsigargin, but are abolished by agents that dissipate storage of by acidic organelles, such as the vacuolar H + pump inhibitor, bafilomycin A1. This has been most clearly demonstrated in the sea urchin egg [28], but also extended to several mammalian cell types [11,[44][45][46]. Two types of pharmacological manipulation of acidic stores have been investigated with regard to NAADP-evoked release. Glycyl-phenylalanyl-naphthylamide (GPN) is an agent that penetrates cellular membranes but is a substrate for the luminal lysosomal enzyme cathepsin C trapping membrane impermeant products within lysosomes resulting in disruption of lysosomal-related organelles by osmotic lysis [47]. T...

NAADP-mediated Ca 2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist

“…Both plant and animal cells have been shown to respond to application of NAADP (reviewed in refs. [12][13][14]. A limited number of reports demonstrated that extracellular stimulation increased intracellular NAADP concentrations, being in accordance with a second messenger function for NAADP (reviewed in refs.…”

NAADP Controls Cross-talk between Distinct Ca2+ Stores in the Heart

“…Nicotinic acid adenine dinucleotide phosphate (NAADP) 2 is a newly discovered Ca 2ϩ messenger with unique properties that has been extensively investigated in various tissues and cell lines (3)(4)(5)(6)(7)(8). Cardiac tissue expresses high affinity binding sites for NAADP, and NAADP stimulates Ca 2ϩ efflux from microsomal fractions derived from rat heart (9).…”

NAADP receptors mediate calcium signaling stimulated by endothelin-1 and norepinephrine in renal afferent arterioles

“…cADPR is produced by plasma membrane-bound ADPR cyclase at relatively neutral physiological pH. NAADP, on the other hand, is primarily generated at very low pH such as that found in lysosomal and endo/exocytic vesicles (16,41). Whereas NAADP may be generated by nonenzymatic means, the ADPR cyclase from the A. californica and the mammalian ADPR cyclase CD38 are the only enzymes currently known to produce NAADP (19,25).…”