Unique kinetics of nicotinic acid–adenine dinucleotide phosphate (NAADP) binding enhance the sensitivity of NAADP receptors for their ligand

Patel, Sandip; Churchill, Grant C.; Galione, Antony

doi:10.1042/bj3520725

Cited by 43 publications

(42 citation statements)

References 23 publications

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“…Radioligand binding studies further suggested that NAADP did not bind to the same site as inositol trisphosphate and cyclic ADP-ribose [15;16]. Bizarrely, NAADP appeared to bind its target in a non-reversible manner [15;17;18] at least in the presence of physiological K + concentrations [19]. This binding site, however, was clearly related to the calcium permeable channel targeted by NAADP, as evidenced by the similar rank order of potency of NAADP analogues for competing with radio-labelled NAADP [20] and for mediating both calcium release and inactivation [21].…”

Section: Naadp Activates a Novel Channelmentioning

confidence: 99%

Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals

2010

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NAADP is a potent regulator of cytosolic calcium levels. Much evidence suggests that NAADP activates a novel channel located on an acidic (lysosomal-like) calcium store, the mobilisation of which results in further calcium release from the endoplasmic reticulum. Here, we discuss the recent identification of a family of poorly characterized ion channels (the two-pore channels) as endo-lysosomal NAADP receptors. The generation of calcium signals by these channels is likened to those evoked by depolarisation during excitation-contraction coupling in muscle. We discuss the idea that two pore-channels can mediate a trigger release of calcium which is then amplified by calcium-induced calcium release from the endoplasmic reticulum. This is similar to the activation of voltage-sensitive calcium channels and subsequent mobilisation of sarcoplasmic reticulum calcium stores in cardiac tissue. We suggest that two-pore channels may physically interact with ryanodine receptors to account for more direct release of calcium from the endoplasmic reticulum in analogy with the conformational coupling of voltage-sensitive calcium channels and ryanodine receptors in skeletal muscle. Interaction of two-pore channels with other calcium release channels likely occurs between stores "trans-chatter" and possibly within the same store "cis-chatter". We also speculate that trafficking of two-pore channels through the endolysosomal system facilitates interactions with calcium entry channels. Strategic placing of two-pore channels thus provides a versatile means of generating spatiotemporally complex cellular calcium signals.

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Section: Naadp Activates a Novel Channelmentioning

confidence: 99%

Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals

2010

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“…Radioligand binding studies employing [ 32 P]NAADP support the idea that NAADP acts on a fundamentally different Ca 2+ releasing channel from those gated by InsP 3 or cADPR. Binding of radiolabelled NAADP to sea urchin egg homogenate membranes is highly specific [13,31,32] and is unaffected by InsP 3 or cADPR [13,31]. Binding studies have revealed another peculiar property of the NAADP receptor where NAADP binds to its receptor in an essentially irreversible manner in the sea urchin egg homogenates [13,31,32].…”

Section: Distinct Properties Of Naadpmentioning

confidence: 99%

“…Binding of radiolabelled NAADP to sea urchin egg homogenate membranes is highly specific [13,31,32] and is unaffected by InsP 3 or cADPR [13,31]. Binding studies have revealed another peculiar property of the NAADP receptor where NAADP binds to its receptor in an essentially irreversible manner in the sea urchin egg homogenates [13,31,32]. In mammalian systems, however, [ 32 P]NAADP binding to membrane preparations from rat brain [31], rat heart [25] and MIN‐6 cells [10] is reversible.…”

Section: Distinct Properties Of Naadpmentioning

confidence: 99%

“…Binding studies have revealed another peculiar property of the NAADP receptor where NAADP binds to its receptor in an essentially irreversible manner in the sea urchin egg homogenates [13,31,32]. In mammalian systems, however, [ 32 P]NAADP binding to membrane preparations from rat brain [31], rat heart [25] and MIN‐6 cells [10] is reversible. The apparent irreversibility of NAADP binding in sea urchin egg preparations is dependent on high K + concentrations in the binding medium routinely used [15].…”

Section: Distinct Properties Of Naadpmentioning

confidence: 99%

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Calcium signalling by nicotinic acid adenine dinucleotide phosphate (NAADP)

2005

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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...

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“…It has been shown previously that, in vitro , NAADP binds to the sea urchin receptor in an irreversible manner under conditions mimicking the cellular environment ( Billington & Genazzani, 2000 ; Patel et al ., 2000 ; Dickinson & Patel, 2003 ). To investigate whether the triazine dyes displayed a similar property, sea urchin egg homogenates were pretreated for 20 min with concentrations of NAADP or dye that, in competition assays, displaced more than 90% of the [ 32 P]NAADP.…”

Section: Resultsmentioning

confidence: 99%

Triazine dyes are agonists of the NAADP receptor

Billington

Bak

Martínez-Coscollá

et al. 2004

British J Pharmacology

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1 NAADP has been shown to be a potent calcium-releasing second messenger in a wide variety of cell types to date. However, research has been hampered by a lack of pharmacological agents, with which to investigate NAADP-induced calcium release, and by the molecular identity of its cellular target protein being unknown. 2 In the present paper, the sea urchin egg model was used to investigate whether triazine dyes, which can act as nucleotide mimetics, can bind to the NAADP receptor, induce Ca 2 þ release and be used for affinity chromatography of the receptor. 3 Indeed, all the triazine dyes tested (Reactive Red 120 (RR120), Reactive Green 19 (RG19), Reactive Green 5 (RG5), Cibacron Blue 3GA and Reactive Yellow 86) displayed micromolar affinities, except for Reactive Orange 14. Furthermore, unlike NAADP, RR120, RG19 and RG5 did not bind in an irreversible manner. 4 The compound that displayed the highest affinity, RR120, was tested in a 45 Ca 2 þ efflux assay. This compound released Ca 2 þ via the NAADP receptor, as shown by the ability of subthreshold NAADP concentrations to inhibit this release. Furthermore, heparin and ruthenium red were unable to block RR120-induced Ca 2 þ release. 5 We have also shown that RG5 and RG19, immobilised on resins, retain the ability to bind to the receptor, and that this interaction can be disrupted by high salt concentrations. As a proof of principle, we have shown that this can be used to partially purify the NAADP receptor by at least 75-fold. 6 In conclusion, triazine dyes interact with the NAADP receptor, and this could be exploited in future to create a new generation of pharmacological tools to investigate this messenger and, in combination with other techniques, to purify the receptor.

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Unique kinetics of nicotinic acid–adenine dinucleotide phosphate (NAADP) binding enhance the sensitivity of NAADP receptors for their ligand

Cited by 43 publications

References 23 publications

Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals

Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals

Calcium signalling by nicotinic acid adenine dinucleotide phosphate (NAADP)

Triazine dyes are agonists of the NAADP receptor

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