Signalling to transcription: Store-operated Ca2+ entry and NFAT activation in lymphocytes

Gwack, Yousang; Feske, Stefan; Srikanth, Sonal; Hogan, Patrick G.; Rao, Anjana

doi:10.1016/j.ceca.2007.03.007

Cited by 270 publications

(254 citation statements)

References 81 publications

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“…Although sustained Ca 2ϩ influx in T-cells has been studied for decades, the proteins involved have only been identified recently (Cahalan et al, 2007;Feske, 2007;Gwack et al, 2007a;Hewavitharana et al, 2007;Hogan and Rao, 2007;Lewis, 2007;Putney, 2007b). Stromal-interacting molecule (STIM) was identified as an essential component for Ca 2ϩ influx through CRAC channels by RNA interference (RNAi) screens in Drosophila and HeLa cells (Liou et al, 2005;Roos et al, 2005 Abbreviations used: APC, antigen-presenting cell; CRAC, Ca 2ϩ release-activated Ca 2ϩ channel; ER, endoplasmic reticulum; FRAP, fluorescence recovery after photobleaching; FRET, Fö rster resonance energy transfer; IS, immunological synapse; MEF, mouse embryonic fibroblast; PM, plasma membrane; TCR, T-cell receptor.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, elevated Ca 2ϩ maintains prolonged nuclear accumulation of nuclear factor of activated T-cells (NFAT) by activating the phosphatase calcineurin that dephosphorylates NFAT, allowing it to translocate to the nucleus and activate genes such as IL2 (Hogan et al, 2003;Macian, 2005). Several hours of Ca 2ϩ influx are required to complete the T-cell activation program, which involves expression of a large number of activation-associated genes (Lewis, 2001;Macian et al, 2002;Hogan et al, 2003).Although sustained Ca 2ϩ influx in T-cells has been studied for decades, the proteins involved have only been identified recently (Cahalan et al, 2007;Feske, 2007;Gwack et al, 2007a;Hewavitharana et al, 2007;Hogan and Rao, 2007;Lewis, 2007;Putney, 2007b). Stromal-interacting molecule (STIM) was identified as an essential component for Ca 2ϩ influx through CRAC channels by RNA interference (RNAi) screens in Drosophila and HeLa cells (Liou et al, 2005;Roos et al, 2005 Abbreviations used: APC, antigen-presenting cell; CRAC, Ca 2ϩ release-activated Ca 2ϩ channel; ER, endoplasmic reticulum; FRAP, fluorescence recovery after photobleaching; FRET, Fö rster resonance energy transfer; IS, immunological synapse; MEF, mouse embryonic fibroblast; PM, plasma membrane; TCR, T-cell receptor.…”

mentioning

confidence: 99%

“…T-cell receptor (TCR) engagement leads to activation of well-documented signal transduction pathways that cause a rapid release of Ca 2ϩ from the endoplasmic reticulum (ER; Samelson, 2002;Panyi et al, 2004;Gwack et al, 2007a). The depletion of Ca 2ϩ from this internal store then leads to the opening of ion channels in the plasma membrane (PM) allowing an influx of Ca 2ϩ from outside the cell.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Barr

Bernot

Srikanth

et al. 2008

MBoC

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129

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The proteins STIM1 and Orai1 are the long sought components of the store-operated channels required in T-cell activation. However, little is known about the interaction of these proteins in T-cells after engagement of the T-cell receptor. We found that T-cell receptor engagement caused STIM1 and Orai1 to colocalize in puncta near the site of stimulation and accumulate in a dense structure on the opposite side of the T-cell. FRET measurements showed a close interaction between STIM1 and Orai1 both in the puncta and in the dense cap-like structure. The formation of cap-like structures did not entail rearrangement of the entire endoplasmic reticulum. Cap formation depended on TCR engagement and tyrosine phosphorylation, but not on channel activity or Ca 2؉ influx. These caps were very dynamic in T-cells activated by contact with superantigen pulsed B-cells and could move from the distal pole to an existing or a newly forming immunological synapse. One function of this cap may be to provide preassembled Ca 2؉ channel components to existing and newly forming immunological synapses. INTRODUCTIONT-cell activation in response to antigen induces and requires the elevation of intracellular Ca 2ϩ (Hogan et al., 2003;Quintana et al., 2005;Feske, 2007). T-cell receptor (TCR) engagement leads to activation of well-documented signal transduction pathways that cause a rapid release of Ca 2ϩ from the endoplasmic reticulum (ER; Samelson, 2002;Panyi et al., 2004;Gwack et al., 2007a). The depletion of Ca 2ϩ from this internal store then leads to the opening of ion channels in the plasma membrane (PM) allowing an influx of Ca 2ϩ from outside the cell. The store-operated channel responsible for Ca 2ϩ influx in T-cells is known as the Ca 2ϩ release-activated Ca 2ϩ (CRAC) channel, which has been studied by electrophysiological techniques for many years (Lewis, 2001;Prakriya and Lewis, 2003;Cahalan et al., 2007;Hewavitharana et al., 2007;Hogan and Rao, 2007;Putney, 2007a).Sustained elevation of cytosolic Ca 2ϩ is required for complete T-cell activation (Iezzi et al., 1998;Lewis, 2001;Hogan et al., 2003;Feske, 2007). High levels of intracellular Ca 2ϩ are necessary to maintain the interaction between a T-cell and antigen-presenting cell (APC) that leads to formation of the specialized contact surface known as the immunological synapse (IS). Increased Ca 2ϩ levels are also required for the activation of transcription factors. In particular, elevated Ca 2ϩ maintains prolonged nuclear accumulation of nuclear factor of activated T-cells (NFAT) by activating the phosphatase calcineurin that dephosphorylates NFAT, allowing it to translocate to the nucleus and activate genes such as IL2 (Hogan et al., 2003;Macian, 2005). Several hours of Ca 2ϩ influx are required to complete the T-cell activation program, which involves expression of a large number of activation-associated genes (Lewis, 2001;Macian et al., 2002;Hogan et al., 2003).Although sustained Ca 2ϩ influx in T-cells has been studied for decades, the proteins involved have only been ident...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Barr

Bernot

Srikanth

et al. 2008

MBoC

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129

140

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“…Signaling from the BCR, 4 which is composed of antigenbinding immunoglobulin (Ig) and signaling Ig␣/Ig␤ subunits, is necessary for the development, differentiation, and activation of B lymphocytes. Tyrosine kinase-dependent activation of phospholipase C-␥2, one of many intracellular signaling events that follow BCR ligation, leads to rapid release of calcium from the lumen of the endoplasmic reticulum into the cytoplasm.…”

mentioning

confidence: 99%

CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor

Polyak¹,

Li²,

Shariat

et al. 2008

Journal of Biological Chemistry

110

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B cell antigen receptor (BCR) signaling initiates sustained cellular calcium influx necessary for the development, differentiation, and activation of B lymphocytes. CD20 is a B cell-restricted tetraspanning protein organized in the plasma membrane as multimeric molecular complexes involved in BCR-activated calcium entry. Using coprecipitation of native CD20 with tagged or truncated forms of the molecule, we provide here direct evidence of CD20 homo-oligomerization into tetramers. Additionally, the function of CD20 was explored by examining its association with surface-labeled and intracellular proteins before and after BCR signaling. Two major surface-labeled proteins that coprecipitated with CD20 were identified as the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR. After activation, BCR-CD20 complexes dissociated, and phosphoproteins and calmodulin-binding proteins were transiently recruited to CD20. These data provide new evidence of the involvement of CD20 in signaling downstream of the BCR and, together with the previously described involvement of CD20 in calcium influx, the first evidence of physical coupling of the BCR to a calcium entry pathway.Signaling from the BCR, 4 which is composed of antigenbinding immunoglobulin (Ig) and signaling Ig␣/Ig␤ subunits, is necessary for the development, differentiation, and activation of B lymphocytes. Tyrosine kinase-dependent activation of phospholipase C-␥2, one of many intracellular signaling events that follow BCR ligation, leads to rapid release of calcium from the lumen of the endoplasmic reticulum into the cytoplasm. Depletion of the intracellular calcium stores triggers a second phase of calcium mobilization, characterized by sustained calcium entry into the cell via plasma membrane-associated "store-operated" calcium entry (SOCE) channels (1, 2). The amplitude and duration of the calcium response is translated into differential gene expression by calcium-sensitive proteins, determining the cellular response to receptor engagement (3-5).Key molecular components of SOCE have recently been identified with the discovery and characterization of the endoplasmic reticulum calcium sensor, STIM1, and the pore-forming subunit of the Icrac channel, Orai1 (2, 4, 6). A point mutation in Orai1 causes a form of hereditary severe combined immune deficiency syndrome, emphasizing the importance of intracellular calcium in lymphocyte physiology. However, although SOCE is absent in T lymphocytes from these patients, SOCE in B lymphocytes is reduced but not abolished, indicating additional SOCE pathways in the B cell lineage (1, 7).Increasing evidence has indicated that CD20, a B cell-restricted member of the MS4A (multispanning 4A) family of tetraspanins, functions in calcium entry. Intracellular calcium levels were increased in non-B cells ectopically expressing CD20 by transfection, and a calcium-mediated current, similar to that observed in B cells, was detected by whole cell patch clamp analysis (8, 9). BCR-activated calcium entry was ...

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“…6, A and C). Because NFAT activation is highly dependent on both InsP 3 -induced intracellular Ca 2ϩ release and store-operated Ca 2ϩ entry mediated by CRAC channels (50,70), it is likely that reductions of both responses participate in reducing nuclear NFAT translocation. Furthermore, analysis of the Ca 2ϩ oscillatory behavior in the absence of extracellular Ca 2ϩ at 40 g/ml anti-IgM revealed that the majority of responses (Ͼ75%) consisted of more than one Ca 2ϩ spike in cells expressing WT PLC␥ 2 , whereas this parameter was reduced to 35% in cells expressing the F897Q mutant, showing only a single Ca 2ϩ spike in most cases (cf.…”

Section: Discussionmentioning

confidence: 99%

Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling

Walliser

Tron

Clauß

et al. 2015

Journal of Biological Chemistry

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Background: Phospholipase C␥ 2 (PLC␥ 2 ) is stimulated by Rac GTPases through direct protein-protein interaction. Results: The Rac-PLC␥ 2 interaction markedly enhances B cell-receptor-mediated Ca 2ϩ mobilization and nuclear translocation of the Ca 2ϩ -regulated transcription factor NFAT in B cells. Conclusion: Rac-mediated stimulation of PLC␥ 2 activity amplifies B cell receptor-induced Ca 2ϩ signaling. Significance: A specific Rac-resistant PLC␥ 2 variant is used to determine the physiological cell signaling relevance of a functional Rac-PLC␥ 2 interaction in an appropriate cellular context.

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Signalling to transcription: Store-operated Ca2+ entry and NFAT activation in lymphocytes

Cited by 270 publications

References 81 publications

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor

Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling

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