A Novel Ca2+ Entry Mechanism Is Turned On during Growth Arrest Induced by Ca2+ Pool Depletion

Ufret-Vincenty, Carmen A.; Short, Alison D.; Alfonso, Amparo; Gill, Donald L.

doi:10.1074/jbc.270.45.26790

Cited by 34 publications

(28 citation statements)

References 23 publications

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“…Ca 2ϩ measurements were as described (11). Fura2͞acetoxymethyl ester loading was for 25 min at 20°C for DT40 cells, 1 h at 20°C for PC12 cells, 25 min at 20°C for HEK293 cells, and 30 min at 20°C for A7r5 cells.…”

Section: Methodsmentioning

confidence: 99%

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Agonist-induced Ca ²⁺ entry determined by inositol 1,4,5-trisphosphate recognition

Rossum

Patterson

Kiselyov

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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It has been considered that Ca 2؉ release is the causal trigger for Ca 2؉ entry after receptor activation. In DT40 B cells devoid of inositol 1,4,5-trisphosphate receptors (IP3R), the lack of Ca 2؉ entry in response to receptor activation is attributed to the absence of Ca 2؉ release. We reveal in this article that IP 3 R recognition of IP 3 determines agonist-induced Ca 2؉ entry (ACE), independent of its Ca 2؉ release activity. In DT40 IP3R ؊/؊ cells, endogenous ACE can be rescued with type 1 IP3R mutants (both a ⌬C-terminal truncation mutant and a D2550A pore mutant), which are defective in Ca 2؉ release channel activity. Thus, in response to B cell receptor activation, ACE is restored in an IP3R-dependent manner without Ca 2؉ store release. Conversely, ACE cannot be rescued with mutant IP3Rs lacking IP3 binding (both the ⌬90 -110 and R265Q IP3-binding site mutants). We conclude that an IP3-dependent conformational change in the IP3R, not endoplasmic reticulum Ca 2؉ pool release, triggers ACE.C a 2ϩ transients elicited in response to cell surface receptor activation by neurotransmitters, hormones, and other molecular messengers are major messengers of intracellular communication (1). Stimulation of G protein-coupled receptors, tyrosine kinase receptors, and nonreceptor tyrosine kinases activate phospholipase C (PLC), catalyzing the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) into the secondmessenger molecules: inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DAG). IP 3 mediates rapid Ca 2ϩ store release by activating IP 3 receptors (IP 3 Rs) in the endoplasmic reticulum (ER), whereas DAG activates protein kinase C (PKC) (2). After this initial Ca 2ϩ release phase, external Ca 2ϩ enters through plasma membrane channels, providing a secondary and more prolonged Ca 2ϩ signal (1), a phenomenon designated here as agonist-induced Ca 2ϩ entry (ACE) (3).To date, the molecular identity of these Ca 2ϩ entry channels as well as their coupling mechanism remain unknown, although several mechanisms have been proposed. Intracellular Ca 2ϩ release through the IP 3 R could trigger ACE by means of capacitative Ca 2ϩ entry (CCE) (4), which can be activated in a PLC-independent manner (3) by the ER Ca 2ϩ pump blocker thapsigargin or the Ca 2ϩ ionophore ionomycin (4, 5). In this scheme, the luminal drop in ER Ca 2ϩ activates ''store-operated'' Ca 2ϩ channels in the plasma membrane, although the basis for this coupling mechanism is entirely unknown. Although the release activity of IP 3 Rs may mediate Ca 2ϩ entry, others have suggested that IP 3 Rs play a conformational role in the coupling process (6, 7). Also, DAG may directly initiate ACE, because DAG can activate overexpressed ''canonical'' transient receptor potential Ca 2ϩ entry channels (TRPC) (8).We recently demonstrated a functional distinction between ACE and CCE based on the requirement of the former for PLC-␥, in a lipase-independent manner (3). However, it is unclear whether endogenous ACE is an integrated process accounting for both receptor an...

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Section: Methodsmentioning

confidence: 99%

“…Rat PC12 cells (passage numbers 6-15), human embryonic kidney (HEK)293 cells, rat aortic smooth muscle A7r5 cells (passage numbers [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25], and DT40 chicken B lymphocyte IP 3 R Ϫ/Ϫ cells were cultured as described (3,9,10).…”

Section: Methodsmentioning

confidence: 99%

Agonist-induced Ca ²⁺ entry determined by inositol 1,4,5-trisphosphate recognition

Rossum

Patterson

Kiselyov

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…The relative percentages of 8Br-cADPR, 8Br-ADPR, and 8Br-AMP present in the supernatants are shown and the HPLC chromatograms of standards for each of the compounds are included for comparison. Finally, we assessed the impact of 8Br-ADPR on Ca 2ϩ influx through SOCs that are activated in response to intracellular Ca 2ϩ store depletion (50). We therefore incubated mouse neutrophils (Fig.…”

Section: An Adpr Analog Specifically Blocks Adpr-gated Cation Entrymentioning

confidence: 99%

Chemotaxis of Mouse Bone Marrow Neutrophils and Dendritic Cells Is Controlled by ADP-Ribose, the Major Product Generated by the CD38 Enzyme Reaction

Partida-Sánchez

Gasser

Fliegert

et al. 2007

The Journal of Immunology

136

152

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The ectoenzyme CD38 catalyzes the production of cyclic ADP-ribose (cADPR) and ADP-ribose (ADPR) from its substrate, NAD+. Both products of the CD38 enzyme reaction play important roles in signal transduction, as cADPR regulates calcium release from intracellular stores and ADPR controls cation entry through the plasma membrane channel TRPM2. We previously demonstrated that CD38 and the cADPR generated by CD38 regulate calcium signaling in leukocytes stimulated with some, but not all, chemokines and controls leukocyte migration to inflammatory sites. However, it is not known whether the other CD38 product, ADPR, also regulates leukocyte trafficking In this study we characterize 8-bromo (8Br)-ADPR, a novel compound that specifically inhibits ADPR-activated cation influx without affecting other key calcium release and entry pathways. Using 8Br-ADPR, we demonstrate that ADPR controls calcium influx and chemotaxis in mouse neutrophils and dendritic cells activated through chemokine receptors that rely on CD38 and cADPR for activity, including mouse FPR1, CXCR4, and CCR7. Furthermore, we show that the calcium and chemotactic responses of leukocytes are not dependent on poly-ADP-ribose polymerase 1 (PARP-1), another potential source of ADPR in some leukocytes. Finally, we demonstrate that NAD+ analogues specifically block calcium influx and migration of chemokine-stimulated neutrophils without affecting PARP-1-dependent calcium responses. Collectively, these data identify ADPR as a new and important second messenger of mouse neutrophil and dendritic cell migration, suggest that CD38, rather than PARP-1, may be an important source of ADPR in these cells, and indicate that inhibitors of ADPR-gated calcium entry, such as 8Br-ADPR, have the potential to be used as anti-inflammatory agents.

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“…Although the effect of caffeine on intracellular Ca 2ϩ levels would usually be related to its ability to diffuse across cell membranes and activate ryanodine receptors (RyRs), causing Ca 2ϩ release as in the above-mentioned studies, there are also studies suggesting caffeine can cause Ca 2ϩ influx through the plasma membrane. Experiments where cytosolic Ca 2ϩ changes were monitored provided evidence for the existence of such a pathway for leech P neurons (43), cultured DDT1MF-2 smooth muscle cells (45), jejunal smooth muscle cells (37), and aortic endothelial cells (9). Furthermore, recordings of a caffeine-activated current passing through the plasma membrane have been reported (e.g., see Refs.…”

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confidence: 99%

Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance

Zhang¹,

Tuft²,

Lifshitz³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Caffeine-activated, large-conductance, nonselective cation channels (LCCs) have been found in the plasma membrane of isolated cardiac myocytes in several species. However, little is known about the effects of opening these channels. To examine such effects and to further understand the caffeine-activation mechanism, we carried out studies using whole-cell patch-clamp techniques with freshly isolated cardiac myocytes from rats and mice. Unlike previous studies, thapsigargin was used so that both the effect of opening LCCs and the action of caffeine were independent of Ca2+ release from intracellular stores. These Ca2+-permeable LCCs were found in a majority of the cells from atria and ventricles, with a conductance of ∼370 pS in rat atria. Caffeine and all its direct metabolic products (theophylline, theobromine, and paraxanthine) activated the channel, while isocaffeine did not. Although they share some similarities with ryanodine receptors (RyRs, the openings of which give rise to Ca2+ sparks), LCCs also showed some different characteristics. With simultaneous Ca2+ imaging and current recording, the localized fluorescence increase due to Ca2+ entry through a single opening of an LCC (SCCaFT) was detected. When membrane potential, instead of current, was recorded, SCCaFT-like fluorescence transients (indicating single LCC openings) were found to accompany membrane depolarizations. To our knowledge, this is the first report directly linking membrane potential changes to a single opening of an ion channel. Moreover, these events in cardiac cells suggest a possible additional mechanism by which caffeine and theophylline contribute to the generation of cardiac arrhythmias.

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A Novel Ca2+ Entry Mechanism Is Turned On during Growth Arrest Induced by Ca2+ Pool Depletion

Cited by 34 publications

References 23 publications

Agonist-induced Ca ²⁺ entry determined by inositol 1,4,5-trisphosphate recognition

Agonist-induced Ca ²⁺ entry determined by inositol 1,4,5-trisphosphate recognition

Chemotaxis of Mouse Bone Marrow Neutrophils and Dendritic Cells Is Controlled by ADP-Ribose, the Major Product Generated by the CD38 Enzyme Reaction

Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance

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A Novel Ca2+ Entry Mechanism Is Turned On during Growth Arrest Induced by Ca2+ Pool Depletion

Cited by 34 publications

References 23 publications

Agonist-induced Ca 2+ entry determined by inositol 1,4,5-trisphosphate recognition

Agonist-induced Ca 2+ entry determined by inositol 1,4,5-trisphosphate recognition

Chemotaxis of Mouse Bone Marrow Neutrophils and Dendritic Cells Is Controlled by ADP-Ribose, the Major Product Generated by the CD38 Enzyme Reaction

Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance

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Agonist-induced Ca ²⁺ entry determined by inositol 1,4,5-trisphosphate recognition

Agonist-induced Ca ²⁺ entry determined by inositol 1,4,5-trisphosphate recognition