The endo-lysosomal system as an NAADP-sensitive acidic Ca2+ store: Role for the two-pore channels

Patel, Sandip; Ramakrishnan, Latha; Rahman, Taufiq; Hamdoun, Amro; Marchant, Jonathan S.; Taylor, Colin W.; Brǎiloiu, Eugen

doi:10.1016/j.ceca.2011.03.011

Cited by 62 publications

(55 citation statements)

References 104 publications

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“…Thus, both Ca 2ϩ entry and Ca 2ϩ release occur downstream of sarcolemmal GPR55 activation in cultured neonatal ventricular cardiomyocytes. In addition to the endo/sarcoplasmic reticulum, which expresses Ca 2ϩ release channels such as IP 3 R and RyR (54), the endolysosomal system also functions as a Ca 2ϩ store involved in Ca 2ϩ mobilization (45,55). Using a pharmacological approach, we demonstrate that Ca 2ϩ release occurs primarily via IP 3 Rs and is further amplified by a RyR-dependent CICR mechanism, whereas the endolysosomal NAADP-dependent Ca 2ϩ stores are not involved.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Deliu²,

Zhang

et al. 2013

Journal of Biological Chemistry

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Background:The LPI-sensitive receptor GPR55 signals through Ca 2ϩ . Results: Activation of sarcolemmal versus intracellular GPR55 mobilizes Ca 2ϩ from distinct pools and associates with cardiomyocyte depolarization and hyperpolarization, respectively. Conclusion: GPR55 location critically affects LPI-induced modulation of cardiomyocyte function. Significance: We identify GPR55 as a new receptor regulating cardiac function at two cellular sites.

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Section: Discussionmentioning

confidence: 99%

“…Importantly, the Ca 2ϩ is released from the endolysosomes via the NAADP-sensitive TPCs (45,55), a signal further amplified by RyR-dependent CICR from the sarcoplasmic reticulum. NAADP-dependent Ca 2ϩ release from acidic stores has been shown to elevate the sarcoplasmic reticulum Ca 2ϩ load, thus enhancing cardiomyocyte contraction (68).…”

Section: Discussionmentioning

confidence: 99%

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Deliu²,

Zhang

et al. 2013

Journal of Biological Chemistry

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“…It was shown to selectively target the lysosome-related organelles rich in Ca 2+ and H + and therefore called acidic Ca 2+ -stores. In hepatocytes they are presented as endo-lysosomal system of the cell [16]. There are many hypotheses about the mechanisms of NAADP action.…”

Section: Resultsmentioning

confidence: 99%

“…The actual data collected on the NAADP-receptors remain disputable. The potential NAADP-sensitive Ca 2+ -channels candidates include TRPML1, TRPM2, TPCs and even RyRs [16,17]. In order to investigate the effects of NAADP in the cell, there was synthesized the selective antagonist of NAADP -NED-19.…”

Section: Resultsmentioning

confidence: 99%

Influence of taurolithocholate 3-sulphate on calcium content in cytosol and store of isolated mice hepatocytes

Bychkova¹

2015

Biol. Stud.

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Momohydroxylated bile acids, including taurolitocholate (TLC) and its 3-sulphate (TLC-S), have been shown to increase [Ca 2+ ] i in cytosol of rat hepatocytes [1,2]. These bile acids mobilize Ca 2+ from the internal pool which is sensitive to inositol trisphosphate (IP 3 ). However, bile-acid mediated Ca 2+ release is independent of IP 3 production. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a nucleotide which can to release calcium from specific type of intracellular store defined as endo-lysosomal system or acidic store. The aim of this study was to examine influence of NED-19 (antagonist of NAADP) on TLC-S-induced change of calcium content in cytosol of and endoplasmic reticulum of isolated mice hepatocytes in order to elucidate the role of acidic store in bile-acid mediated Ca 2+ release. Isolated hepatocytes of mice were loaded with fluo-4 (2.5 µM). Fluorescent images were obtained using Leica SP2 MP dual two-photon confocal microscope. Isolated hepatocytes were permeabilized in suspension with saponine (0.1 mg/mL). Next the permeabilized suspension of hepatocytes was loaded with Mag-Fura-2 AM (5 µM). Measurement of Ca2+ content in store of permeabilized cells was conducted using spectrofluorimetric method. We confirmed that TLC-S (50, 100 and 200 µM) elicited cytosolic Ca 2+ -signals, which were not inhibited by the IP 3 -receptors (IP 3 Rs) antagonist 2-APB (100 µM). In suspensions of permeabilized murine hepatocytes TLC-S (100 µM) mobilized 66.10 ± 8.87 % of the total stored calcium as detected by ionomycin-induced release (10 µM). After application of TLC-S thapsigargin could release only 47.94 ± 3.05 %. Previous addition of NED-19 (100 nM) decreased fraction of calcium that is released by TLC-S and equals 33.25 ± 2.15 % of the total calcium. In this case, the following use of thapsigargin mobilized only 21.75 ± 10.68 %. Thus, previous application of NED-19 significantly (n = 6; P ≤ 0.01) reduced the proportion of calcium released by TLC-S 2-fold. It was observed that the rate of TLC-S-induced decrease of calcium content in the intracellular store was 1.8 times slower than after application of NED-19 (n = 6; Р ≤ 0.05). Previous application of NED-19 increased the rate of thapsigargin-evoked calcium content reduction by a factor of 2.5 (n = 6; Р ≤ 0.01). We suggest the impact of acid store in TLC-Selicited cytosolic Ca 2+ -signals in mice hepatocytes. Thus, the mechanism of TLC-S-induced calcium release is also NAADP-mediated.

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“…4,10,60,[69][70][71] Soon after, TPCs were also described as PtdIns(3,5)P2-regulated Na C selective channels, 5,6 and, again, overexpression of TPCs stimulated the PI(3,5)P2-induced current, while this current was abrogated in double-KO mice lacking TPC1 and TPC2. 5,6,71 Nowadays, different molecules have been suggested as regulators of TPCs activity.…”

Section: Activity Regulationmentioning

confidence: 99%

Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions

Feijóo‐Bandín¹,

García-Vence²,

García-Rúa³

et al. 2016

Channels

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Two-pore channels (TPC1-3) comprise a subfamily of the eukaryotic voltage-gated ion channels (VGICs) superfamily that are mainly expressed in acidic stores in plants and animals. TPCS are widespread across the animal kingdom, with primates, mice and rats lacking TPC3, and mainly act as Ca C and Na C channels, although it was also suggested that they could be permeable to other ions. Nowadays, TPCs have been related to the development of different diseases, including Parkinsons disease, obesity or myocardial ischemia. Due to this, their study has raised the interest of the scientific community to try to understand their mechanism of action in order to be able to develop an efficient drug that could regulate TPCs activity. In this review, we will provide an updated view regarding TPCs structure, function and activation, as well as their role in different pathophysiological processes.

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The endo-lysosomal system as an NAADP-sensitive acidic Ca2+ store: Role for the two-pore channels

Cited by 62 publications

References 104 publications

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Influence of taurolithocholate 3-sulphate on calcium content in cytosol and store of isolated mice hepatocytes

Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions

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