A store-operated nonselective cation channel in lymphocytes is activated directly by Ca<sup>2+</sup> influx factor and diacylglycerol

Su, Zhengchang; Csutora, Péter; Hunton, Dacia L.; Shoemaker, R. L.; Marchase, Richard B.; Blalock, J. Edwin

doi:10.1152/ajpcell.2001.280.5.c1284

Cited by 40 publications

(44 citation statements)

References 37 publications

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“…The signal transduction pathway responsible for activating NSCCs involves PLC␥-2 and its product diacylglycerol (DAG). This is consistent with previous studies of lymphocytes that suggest DAG is capable of inducing store-independent Ca 2ϩ influx (13). Paradoxically, BCR engagement, which also activates PLC␥-2 and elicits CRAC-like currents, does not activate NSCCs, but instead suppresses NSCC activation and functions of B cells uniquely regulated by NSCCs.…”

Section: Nels In B Cells Is An Open Question Given Studies Of Patiensupporting

confidence: 92%

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Liu

Wen

et al. 2005

The Journal of Immunology

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Intracellular Ca2+ plays a central role in controlling lymphocyte function. Nonetheless, critical gaps remain in our understanding of the mechanisms that regulate its concentration. Although Ca2+-release-activated calcium (CRAC) channels are the primary Ca2+ entry pathways in T cells, additional pathways appear to be operative in B cells. Our efforts to delineate these pathways in primary murine B cells reveal that Ca2+-permeant nonselective cation channels (NSCCs) operate in a cooperative fashion with CRAC. Interestingly, these non-CRAC channels are selectively activated by mechanical stress, although the mechanism overlaps with BCR-activated pathways, suggesting that they may operate in concert to produce functionally diverse Ca2+ signals. NSCCs also regulate the membrane potential, which activates integrin-dependent binding of B cells to extracellular matrix elements involved in their trafficking and localization within secondary lymphoid organs. Thus, CRAC and distinct Ca2+ permeant NSCCs are differentially activated by the BCR and mechanical stimuli and regulate distinct aspects of B cell physiology.

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Section: Nels In B Cells Is An Open Question Given Studies Of Patiensupporting

confidence: 92%

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Liu

Wen

et al. 2005

The Journal of Immunology

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“…55 This hypothesis is confirmed by the fact that lanthanum, a selective inhibitor of store-operated calcium channels (I CRAC ), 56 but not voltage-dependent calcium channel blockers like nifedipine or verapamil (data not shown), inhibited the action of CALP2. Furthermore, I CRAC channels are present in macrophages and neutrophils but not in eosinophils 57,58 Since CALP2 did not activate eosinophils, this further strengthens the hypothesis that CALP2, at least partly, acts via (store-operated) calcium channels.…”

Section: Discussionmentioning

confidence: 84%

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Broeke

Leusink-Muis

Hilberdink

et al. 2004

Laboratory Investigation

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Airway inflammation is a characteristic feature in airway diseases such as asthma and chronic obstructive pulmonary disease. Oxidative stress, caused by the excessive production of reactive oxygen species by inflammatory cells like macrophages, eosinophils and neutrophils, is thought to be important in the complex pathogenesis of such airway diseases. The calcium-sensing regulatory protein calmodulin (CaM) binds and regulates different target enzymes and proteins, including calcium channels. In the present study, we investigated whether CaM, via the modulation of calcium channel function, influences [Ca 2 þ ] i in pulmonary inflammatory cells, and consequently, modulates the production of reactive oxygen species by these cells. This was tested with a peptide termed calcium-like peptide 2 (CALP2), which was previously shown to regulate such channels. Specifically, radical production by purified broncho-alveolar lavage cells from guinea-pigs in response to CALP2 was measured. CALP2 was a strong activator of alveolar macrophages. In contrast, CALP2 was only a mild activator of neutrophils and did not induce radical production by eosinophils. The CALP2-induced radical production was mainly intracellular, and was completely blocked by the NADPH-oxidase inhibitor DPI, the superoxide inhibitor SOD and the CaM antagonist W7. Furthermore, the calcium channel blocker lanthanum partly inhibited the cellular activation by CALP2. We conclude that alveolar macrophages, but not neutrophils or eosinophils, can produce extremely high amounts of reactive oxygen species when stimulated via the calcium/CaM pathway. These results may contribute to new therapeutic strategies against oxidative stress in airway diseases.

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“…There are reports in the literature of endogenous channels that could fit either behavior, e.g. storeoperated non-selective cations channels (30), including the suggestion of a channel that can be regulated by both storedepletion and DAG (31), and receptor-and DAG-activated non-selective cation channels (32,33). Thus, for the moment, we may consider the intriguing possibility that either or even both of these TRPC3 behaviors correspond to a physiological mode of TRPC3 channel regulation, depending on the specific cellular environment.…”

Section: Figmentioning

confidence: 99%

Expression Level of the Canonical Transient Receptor Potential 3 (TRPC3) Channel Determines Its Mechanism of Activation

Vázquez

Wedel

Trebak

et al. 2003

Journal of Biological Chemistry

148

122

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Studies on the mechanism of activation of canonical transient receptor potential (TRPC) channels have often yielded conflicting results. In the current study, we have investigated the influence of expression level on the mode of regulation of TRPC3 channels. At relatively low levels of expression in DT40 chicken B-lymphocytes, TRPC3 was activated by the depletion of Ca 2؉ stores. Expression was increased by either transfecting with a 10-fold greater concentration of plasmid or transfecting with TRPC3 under control of a more efficient avian ␤-actin promoter. At higher levels of expression, TRPC3 was no longer store-operated but could be activated through receptor-coupled phospholipase C. Under these expression conditions, TRPC3 was efficiently activated in DT40 cells lacking inositol 1,4,5-trisphosphate receptors. The Ca 2؉ store-operated channels formed upon expression of TRPC3 at limited levels were blocked by gadolinium; the receptor-activated channels formed upon expression of higher levels of TRPC3 were insensitive to gadolinium. These findings indicate that a single ion channel protein can form or contribute to the formation of channels regulated in two very distinct ways, i.e. either by phospholipase C-derived messengers or Ca 2؉ store-depletion. The mechanism of regulation of the channels depends on their level of expression.In most nonexcitable cells, calcium signaling initiated through cell membrane receptors coupled to phospholipase C (PLC) 1 results in production of inositol 1,4,5-trisphosphate (IP 3 ) (1, 2). IP 3 induces the release of Ca 2ϩ from the endoplasmic reticulum and the subsequent influx of Ca 2ϩ across the plasma membrane through the capacitative calcium entry (CCE) or the store-operated calcium entry pathway (3-6). Although CCE has been widely studied in diverse cell types, the molecular identity of store-operated channels (SOCs) and the signal by which store emptying activates those channels remain uncertain. Mammalian homologues of the Drosophila transient receptor potential (TRP) channel have been proposed as candidates for SOCs (7,8). Among the members of the canonical TRP (TRPC) subfamily (designated TRPC1 through TRPC7), human TRPC3, first cloned by Zhu et al. (9), has been shown in many heterologous expression systems to behave as a receptor-activated channel with constitutive activity that cannot be further increased by Ca 2ϩ store depletion (10 -12). Furthermore, Hofmann et al. (13) showed that TRPC3 and its structural relative TRPC6 can be activated by diacylglycerols (DAGs), providing a possible mechanism of activation of these channels by phospholipase C-linked receptors independent of IP 3 and store depletion.We recently demonstrated that TRPC3 is regulated by store depletion when transiently expressed in DT40 chicken B-lymphocytes (14), and we proposed TRPC3 as a candidate for store-operated, non-selective cation channels. However, Venkatachalam et al. (15) reported that, in this same cell line, TRPC3 behaves as a receptor-activated channel with no dependence on the deple...

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A store-operated nonselective cation channel in lymphocytes is activated directly by Ca²⁺ influx factor and diacylglycerol

Cited by 40 publications

References 37 publications

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Expression Level of the Canonical Transient Receptor Potential 3 (TRPC3) Channel Determines Its Mechanism of Activation

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A store-operated nonselective cation channel in lymphocytes is activated directly by Ca2+ influx factor and diacylglycerol

Cited by 40 publications

References 37 publications

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Expression Level of the Canonical Transient Receptor Potential 3 (TRPC3) Channel Determines Its Mechanism of Activation

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A store-operated nonselective cation channel in lymphocytes is activated directly by Ca²⁺ influx factor and diacylglycerol