Physiological roles of NAADP-mediated Ca2+ signaling

Galione, Antony; Parrington, John; Funnell, Tim M.

doi:10.1007/s11427-011-4207-5

Cited by 26 publications

(28 citation statements)

References 81 publications

(78 reference statements)

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“…4 is a potent Ca 2ϩ -releasing messenger that has been shown to regulate many physiological processes encompassing fertilization, secretion, neurite outgrowth, and synaptic function (1)(2)(3)(4). Although molecular identification of the Ca 2ϩ channel(s) targeted by NAADP remained frustratingly elusive for many years, several lines of evidence have recently unmasked the two-pore channel (TPC) family of endolysosomal proteins as candidate NAADP receptors (5-7).…”

Section: Naadpmentioning

confidence: 99%

Photoaffinity Labeling of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Targets in Mammalian Cells*

Lin-Moshier

Walseth

Churamani

et al. 2012

Journal of Biological Chemistry

156

159

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Section: Naadpmentioning

confidence: 99%

Photoaffinity Labeling of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Targets in Mammalian Cells*

Lin-Moshier

Walseth

Churamani

et al. 2012

Journal of Biological Chemistry

156

159

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“…Cytosolic calcium can also increase in response to the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) (21-24). NAADP releases calcium from acidic endolysosomal stores (21)(22)(23)(25)(26)(27)(28) by activation of two-pore channels (29 -31). Since its discovery by Lee and colleagues (17,22) almost 20 years ago, the emerging consensus is that NAADP is a widespread messenger that plays physiological roles in many mammalian systems (6,21,23,24,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41).…”

mentioning

confidence: 99%

“…NAADP releases calcium from acidic endolysosomal stores (21)(22)(23)(25)(26)(27)(28) by activation of two-pore channels (29 -31). Since its discovery by Lee and colleagues (17,22) almost 20 years ago, the emerging consensus is that NAADP is a widespread messenger that plays physiological roles in many mammalian systems (6,21,23,24,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41).In airway smooth muscle contraction, both IP 3 and cyclic ADP-ribose and their signaling components have been reported and well characterized (3,5,6,8,12,13,34), but a role for NAADP in this muscle type has not been reported. One study did investigate a role for NAADP in tracheal smooth muscle but reported negative results (42).…”

mentioning

confidence: 99%

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Is a Second Messenger in Muscarinic Receptor-induced Contraction of Guinea Pig Trachea

Aley

Singh

Brailoiu

et al. 2013

Journal of Biological Chemistry

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Background: NAADP is a messenger that links cell surface receptors to contraction in many cells, but its function is unknown in tracheal contraction. Results: NAADP participates in contractions induced by a neurotransmitter receptor. Conclusion: NAADP is a messenger that mediates tracheal contraction. Significance: Inappropriate tracheal contractions underlie asthma, and NAADP represents a new physiological mediator and drug target. Nicotinic acid adenine dinucleotide phosphate (NAADP) isincreasingly being demonstrated to be involved in calcium signaling in many cell types and species. Although it has been shown to play a role in smooth muscle cell contraction in several tissues, nothing is known about its possible role in tracheal smooth muscle, a muscle type that is clinically relevant to asthma. To determine whether NAADP functions as a second messenger in tracheal smooth muscle contraction, we used the criteria set out by Sutherland for a molecule to be designated a second messenger. We report that NAADP satisfies all five criteria as follows. First, the NAADP antagonist Ned-19 inhibited contractions in tracheal rings and calcium increases in isolated smooth muscle cells induced by the muscarinic agonist carbachol. Second, NAADP increased cytosolic calcium in isolated cells when microinjected and was blocked by Ned-19. Third, tracheal homogenates could synthesize NAADP by base exchange from exogenous NADP and nicotinic acid and metabolize exogenous NAADP to nicotinic acid adenine dinucleotide by a 2 -phosphatase. Fourth, carbachol induced a rapid and transient increase in endogenous NAADP levels. Fifth, tracheal homogenates contained NAADP-binding sites of high affinity. Taken together, these data demonstrate that NAADP functions as a second messenger in tracheal smooth muscle, and therefore, steps in the NAADP signaling pathway might provide possible new drug targets.Airway diameter is dynamically regulated during normal physiological processes, but inappropriate narrowing caused by hyperresponsiveness results in asthma. Airway contractility is mediated by smooth muscle contraction, which is largely driven by increases in cytosolic calcium, as in other types of smooth muscle (1-6). Smooth muscle relaxation can occur through either a decrease in calcium or an increase in cyclic AMP (7). The G-protein-coupled receptors linked to cytosolic calcium and cyclic AMP have been intensively characterized not only for a better understanding of the basic biology but also because this biological knowledge can be exploited to provide pharmacological treatments (7-11).Cytosolic calcium can increase through either release from intracellular stores or influx from the extracellular space (3,(12)(13)(14)(15)(16). Traditionally, focus has been on calcium stored in the sarcoplasmic reticulum (12, 13), which is released through channels, either inositol 1,4,5-trisphosphate (IP 3 ) 3 receptors activated by IP 3 (12, 13) or ryanodine receptors activated by cyclic . Cytosolic calcium can also increase in response to the second mess...

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“…Recent studies indicate that NAADP acts upon a novel family of endo-lysosomal channels in animal cells termed two-pore channels (TPCs) [20,21]. Galione et al [22] then summarized the physiological roles of NAADPmediated Ca 2+ signalling. They provided a historical perspective on the research of TPCs, studies on which unveiled the physiological role of NAADP as an intracellular Ca 2+ mobilizing messenger.…”

mentioning

confidence: 99%

On Ca2+ signalling research

Leng

2012

Sci. China Life Sci.

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Physiological roles of NAADP-mediated Ca2+ signaling

Cited by 26 publications

References 81 publications

Photoaffinity Labeling of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Targets in Mammalian Cells*

Photoaffinity Labeling of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Targets in Mammalian Cells*

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Is a Second Messenger in Muscarinic Receptor-induced Contraction of Guinea Pig Trachea

On Ca2+ signalling research

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