Orai1-NFAT Signalling Pathway Triggered by T Cell Receptor Stimulation

Srikanth, Sonal; Gwack, Yousang

doi:10.1007/s10059-013-0073-2

Cited by 89 publications

(81 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we currently do not know the significance of this interaction, it is additionally possible that Ca 2ϩ entry through ASIC1 directly activates calcineurin. Several studies provide evidence that Ca 2ϩ store depletion triggers the dynamic recruitment of AKAP79/calcineurin to activated store-operated channel complexes (29,37,40,41). This is an area that we are currently investigating in more detail.…”

Section: Discussionmentioning

confidence: 90%

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Herbert

Nitta

Yellowhair

et al. 2016

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Herbert LM, Nitta CH, Yellowhair TR, Browning C, Gonzalez Bosc LV, Resta TC, Jernigan NL. PICK1/calcineurin suppress ASIC1-mediated Ca 2ϩ entry in rat pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol 310: C390 -C400, 2016. First published December 23, 2015; doi:10.1152/ajpcell.00091.2015.-Acidsensing ion channel 1 (ASIC1) contributes to Ca 2ϩ influx and contraction in pulmonary arterial smooth muscle cells (PASMC). ASIC1 binds the PDZ (PSD-95/Dlg/ZO-1) domain of the protein interacting with C kinase 1 (PICK1), and this interaction is important for the subcellular localization and/or activity of ASIC1. Therefore, we first hypothesized that PICK1 facilitates ASIC1-dependent Ca 2ϩ influx in PASMC by promoting plasma membrane localization. Using Duolink to determine protein-protein interactions and a biotinylation assay to assess membrane localization, we demonstrated that the PICK1 PDZ domain inhibitor FSC231 diminished the colocalization of PICK1 and ASIC1 but did not limit ASIC1 plasma membrane localization. Although stimulation of store-operated Ca 2ϩ entry (SOCE) greatly enhanced colocalization between ASIC1 and PICK1, both FSC231 and shRNA knockdown of PICK1 largely augmented SOCE. These data suggest PICK1 imparts a basal inhibitory effect on ASIC1 Ca 2ϩ entry in PASMC and led to an alternative hypothesis that PICK1 facilitates the interaction between ASIC1 and negative intracellular modulators, namely PKC and/or the calcium-calmodulin-activated phosphatase calcineurin. FSC231 limited PKC-mediated inhibition of SOCE, supporting a potential role for PICK1 in this response. Additionally, we found PICK1 inhibits ASIC1-mediated SOCE through an effect of calcineurin to dephosphorylate the channel. Furthermore, it appears PICK1/calcineurin-mediated regulation of SOCE opposes PKA phosphorylation and activation of ASIC1. Together our data suggest PKA and PICK1/calcineurin differentially regulate ASIC1-mediated SOCE and these modulatory complexes are important in determining downstream Ca 2ϩ signaling.store-operated calcium entry; FSC231; DEG/ENaC; Duolink; PKA; PKC ACID-SENSING ION CHANNELS (ASIC) belong to the degenerin/ epithelial sodium channel (DEG/ENaC) superfamily, which includes several amiloride-sensitive cation channels. Significant progress has been made in understanding the structure and function of ASIC in the nervous system; however, several questions remain regarding their physiological importance in other tissues. There is an emerging role for both ENaC and ASIC in vascular smooth muscle and endothelial cells from a variety of vascular beds (8, 10 -12, 19, 20, 25, 33, 46). Consistent with a physiological role of ASIC in the vasculature, our laboratory has recently shown that ASIC1 is an important facilitator of G protein-coupled receptor signaling via store-operated Ca 2ϩ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMC) (21, 22). Furthermore, ASIC1-mediated Ca 2ϩ entry in PASMC appears to be an important constituent of both the active vasoconstrictor and vascular remodelin...

show abstract

Section: Discussionmentioning

confidence: 90%

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Herbert

Nitta

Yellowhair

et al. 2016

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Over the past two decades, Ca 2+ entry through CRAC channels has become appreciated as a ubiquitous receptor-regulated, PLC-dependent Ca 2+ entry pathway that controls various physiological functions in different cellular systems (Cahalan et al, 2007;Hogan and Rao, 2007;Lewis, 2011;Courjaret and Machaca, 2012;Feske et al, 2012;Trebak, 2012;Lompre et al, 2013;Srikanth and Gwack, 2013). The mechanisms of activation of store-dependent CRAC channels have been intensely studied over the past 7 years and are therefore relatively well understood (Lewis, 2011;Derler et al, 2012;Srikanth and Gwack, 2012;Prakriya, 2013).…”

Section: Introductionmentioning

confidence: 99%

Complex role of STIM1 in the activation of store-independent Orai1/3 channels

Zhang¹,

Zhang²,

González-Cobos³

et al. 2014

J Cell Biol

View full text Add to dashboard Cite

Orai proteins contribute to Ca 2+ entry into cells through both store-dependent, Ca 2+ release-activated Ca 2+ (CRAC) channels (Orai1) and store-independent, arachidonic acid (AA)-regulated Ca 2+ (ARC) and leukotriene C 4 (LTC 4 )-regulated Ca 2+ (LRC) channels (Orai1/3 heteromultimers). Although activated by fundamentally different mechanisms, CRAC channels, like ARC and LRC channels, require stromal interacting molecule 1 (STIM1). The role of endoplasmic reticulum-resident STIM1 (ER-STIM1) in CRAC channel activation is widely accepted. Although ER-STIM1 is necessary and sufficient for LRC channel activation in vascular smooth muscle cells (VSMCs), the minor pool of STIM1 located at the plasma membrane (PM-STIM1) is necessary for ARC channel activation in HEK293 cells. To determine whether ARC and LRC conductances are mediated by the same or different populations of STIM1, Orai1, and Orai3 proteins, we used whole-cell and perforated patch-clamp recording to compare AA-and LTC 4 -activated currents in VSMCs and HEK293 cells. We found that both cell types show indistinguishable nonadditive LTC 4 -and AA-activated currents that require both Orai1 and Orai3, suggesting that both conductances are mediated by the same channel. Experiments using a nonmetabolizable form of AA or an inhibitor of 5-lipooxygenase suggested that ARC and LRC currents in both cell types could be activated by either LTC 4 or AA, with LTC 4 being more potent. Although PM-STIM1 was required for current activation by LTC 4 and AA under whole-cell patch-clamp recordings in both cell types, ER-STIM1 was sufficient with perforated patch recordings. These results demonstrate that ARC and LRC currents are mediated by the same cellular populations of STIM1, Orai1, and Orai3, and suggest a complex role for both ER-STIM1 and PM-STIM1 in regulating these store-independent Orai1/3 channels.

show abstract

“…The aberrant skin barrier in AD is more susceptible to penetration by allergens and chemical irritants; this induces proliferation of keratinocytes and dendritic cells and production of proinflammatory cytokines, such as thymic stromal lymphopoietin (TSLP), which activates and recruits CD4 + T cells (Boguniewicz and Leung, 2011). In T cells, ORAI1 is activated via antigen receptors, increasing intracellular Ca 2+ concentration, which subsequently activates nuclear factor of activated T cells (NFAT) to produce Th2 cytokines (IL-2, IL-4, and IL-13) (Srikanth and Gwack, 2013). In mast cells, the high-affinity IgE receptor activates ORAI1 channels, resulting in the release of proinflammatory mediators (histamine and leukotriene C4 (LTC 4 )), which induces an allergic response (Di Capite et al, 2011).…”

Section: Effect Of Pc and Bc Extracts On I Orai1 Activitymentioning

confidence: 99%

Modulatory Effect of Periostracum Cicadae and Betulae Cortex Extracts on the Activation of Atopic Dermatitis-Related Ion Channels Orai1 and Trpv3

Nam

Jung²,

Kim³

et al. 2017

Afr J Tradit Complement Altern Med

View full text Add to dashboard Cite

Background: The cast-off shells of Cryptotympana pustulata (Periostracum Cicadae, PC) and the bark of Betula platyphylla (Betulae Cortex, BC) are used as traditional medicines for the treatment of skin diseases. This study was conducted to investigate the regulatory effects of PC and BC extracts on the activation of the ion channels, calcium release-activated calcium channel protein 1 (ORAI1) and transient receptor potential cation channel subfamily V member 3 (TRPV3). Materials and Methods: Human HEK293T cells, co-overexpressing ORAI1/stromal interaction molecule 1 (STIM1) or overexpressing TRPV3, were treated with PC or BC extracts at 0.1 mg/mL. The changes in ORAI1 and TRPV3 activities were measured using a conventional whole-cell patch-clamp technique. Results: PC and BC extracts significantly decreased ORAI1 activation in ORAI1-STIM1 co-overexpressing HEK293T cells and significantly increased TRPV3 activation in TRPV3 overexpressing cells, compared to that of 2-aminoethoxydiphenyl borate (2-APB, 100 µM), a known agonist of TRPV3. Conclusion: Our results suggest that PC and BC extracts have therapeutic potential to improve skin barrier abnormalities in atopic dermatitis via modulation of ORAI1 and TRPV3 activation.

show abstract

Orai1-NFAT Signalling Pathway Triggered by T Cell Receptor Stimulation

Cited by 89 publications

References 132 publications

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Complex role of STIM1 in the activation of store-independent Orai1/3 channels

Modulatory Effect of Periostracum Cicadae and Betulae Cortex Extracts on the Activation of Atopic Dermatitis-Related Ion Channels Orai1 and Trpv3

Contact Info

Product

Resources

About

Orai1-NFAT Signalling Pathway Triggered by T Cell Receptor Stimulation

Cited by 89 publications

References 132 publications

PICK1/calcineurin suppress ASIC1-mediated Ca2+ entry in rat pulmonary arterial smooth muscle cells

PICK1/calcineurin suppress ASIC1-mediated Ca2+ entry in rat pulmonary arterial smooth muscle cells

Complex role of STIM1 in the activation of store-independent Orai1/3 channels

Modulatory Effect of Periostracum Cicadae and Betulae Cortex Extracts on the Activation of Atopic Dermatitis-Related Ion Channels Orai1 and Trpv3

Contact Info

Product

Resources

About

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells