Local Ca2+ Influx through Ca2+ Release-activated Ca2+ (CRAC) Channels Stimulates Production of an Intracellular Messenger and an Intercellular Pro-inflammatory Signal

Chang, Wei Chiao; Capite, Joseph L. di; Singaravelu, Karthika; Nelson, Charmaine; Halse, Victoria; Parekh, Anant B.

doi:10.1074/jbc.m705002200

Cited by 72 publications

(90 citation statements)

References 39 publications

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“…Such Ca 2 þ microdomains are associated with SOCE and activate co-localized effectors, including volume-activated anion channel 54 , Ca 2 þ -dependent adenylate cyclase [55][56][57] , phospholipase A2 (cPLA2), and 5-lipoxygenase to generate the pro-inflammatory leukotriene LTC4 in mast cells 5,58 . In fact adenylate cyclase-8 directly interacts with Orai1 59 , explaining its exquisite activation through SOCE.…”

Section: Discussionmentioning

confidence: 99%

Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

Courjaret

Machaca

2014

Nat Commun

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The versatility and universality of Ca 2 þ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca 2 þ signalling is well studied in the microdomain scale, close to a Ca 2 þ channel, and at the whole-cell level. However, little is known about how local Ca 2 þ signals are regulated to specifically activate spatially distant effectors without a global Ca 2 þ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP 3 ) receptor, SERCA pump and store-operated Ca 2 þ entry (SOCE) allows for efficient mid-range Ca 2 þ signalling. Ca 2 þ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP 3 Rs to activate distal Ca 2 þ -activated Cl À channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP 3 R limits local Ca 2 þ diffusion and funnels Ca 2 þ through the ER lumen to activate a spatially separate Ca 2 þ effector.

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Section: Discussionmentioning

confidence: 99%

Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

Courjaret

Machaca

2014

Nat Commun

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“…Ca 2ϩ Imaging-Ca 2ϩ imaging experiments were carried out using the IMAGO CCD camera-based system from TILL Photonics, as described previously using Fura 5F (loaded in the AM form) (18). Cells were alternately excited at 356 and 380 nm (20-ms exposures; 0.5 Hz) using a polychrome monochromator.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the non-receptor tyrosine kinase Syk clusters at the cell periphery and couples Ca 2ϩ microdomains to c-fos expression through recruitment of the cytoplasmic transcription factor STAT5 in a protein kinase C-and MEK/ERK-independent pathway. Ca 2ϩ microdomains following CRAC channel activation also activate Ca 2ϩ -dependent phospholipase A 2 , followed by secretion of cysteinyl leukotrienes (18). However, unlike c-fos expression, this is mediated via the MEK/ERK pathway.…”

Section: Camentioning

confidence: 99%

Coupling of Ca2+ Microdomains to Spatially and Temporally Distinct Cellular Responses by the Tyrosine Kinase Syk

Nelson

Parekh

2009

Journal of Biological Chemistry

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microdomain, which occurs following the opening of a Ca 2ϩ -permeable channel in either the plasma membrane or intracellular organelles (5). Because the volume a microdomain occupies is extremely small, the Ca 2ϩ concentration can rise to reach levels that are orders of magnitude greater than the bulk cytoplasmic Ca 2ϩ rise (3, 5). Store-operated Ca 2ϩ channels are the major route for agonist-evoked Ca 2ϩ entry in non-excitable cells and open following stimulation of phospholipase C-coupled receptors (6). These receptors generate inositol 1,4,5-trisphosphate, which releases Ca 2ϩ from the endoplasmic reticulum (ER) 3 (7). The fall in Ca 2ϩ content within the store is detected by the ER Ca 2ϩ sensor STIM1, which migrates to specialized ER-plasma membrane junctions, where it opens the storeoperated channels (8). The best characterized store-operated channel is the Ca 2ϩ release-activated Ca 2ϩ (CRAC) channel (6), the pore-forming subunit of which is composed of Orai1 (9 -12). Ca 2ϩ entry through CRAC channels regulates enzyme activity, secretion, gene expression, and cell growth and proliferation (13).Here, we have examined whether excitation-transcription coupling is driven by Ca 2ϩ microdomains arising from open CRAC channels in mast cells. In T cells, NFAT-dependent gene expression requires a global Ca 2ϩ rise (14 -16). We find that local Ca 2ϩ influx signals to the nucleus much more effectively than a robust bulk Ca 2ϩ rise. This leads to the expression of the transcription factor c-fos, a regulator of proinflammatory gene expression (17). Furthermore, the non-receptor tyrosine kinase Syk clusters at the cell periphery and couples Ca 2ϩ microdomains to c-fos expression through recruitment of the cytoplasmic transcription factor STAT5 in a protein kinase C-and MEK/ERK-independent pathway. Ca 2ϩ microdomains following CRAC channel activation also activate Ca 2ϩ -dependent phospholipase A 2 , followed by secretion of cysteinyl leukotrienes (18). However, unlike c-fos expression, this is mediated via the MEK/ERK pathway. Parallel processing of the Ca 2ϩ microdomain by Syk through two distinct signaling pathways constitutes a novel mechanism to evoke spatially and temporally different cellular responses. EXPERIMENTAL PROCEDURESCell Culture-Rat basophilic leukemia-1 (RBL-1), an immortalized mast cell line, was bought from ATCC. Cells were cultured (37°C, 5% CO 2 ) in Dulbecco's modified Eagle's medium with 10% fetal bovine serum, 2 mM L-glutamine, and penicillin/ streptomycin, as described previously (19). For Ca 2ϩ imaging and patch clamp experiments, cells were passaged (using trypsin) onto glass coverslips and used 24 -48 h after plating. All cells were used between passages 4 and 16.Ca 2ϩ Imaging-Ca 2ϩ imaging experiments were carried out using the IMAGO CCD camera-based system from TILL Photonics, as described previously using Fura 5F (loaded in the AM form) (18). Cells were alternately excited at 356 and 380 nm (20-ms exposures; 0.5 Hz) using a polychrome monochromator. Images were analyzed offline using IGOR ...

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“…SOCE has been shown to activate or repress particular enzymes with high specificity, including adenylate cyclases (Willoughby and Cooper 2007), the plasma membrane Ca 2þ pump (Bautista and Lewis 2004), and phospholipase A 2 (Chang et al 2008). The evidence for local signaling is mostly based on two approaches.…”

Section: Future Directions Formation and Function Of The Er-pm Junctionsmentioning

confidence: 99%

Store-Operated Calcium Channels: New Perspectives on Mechanism and Function

Lewis¹

2011

Cold Spring Harbor Perspectives in Biology

178

201

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Store-operated calcium channels (SOCs) are a nearly ubiquitous Ca 2þ entry pathway stimulated by numerous cell surface receptors via the reduction of Ca 2þ concentration in the ER. The discovery of STIM proteins as ER Ca 2þ sensors and Orai proteins as structural components of the Ca 2þ release-activated Ca 2þ (CRAC) channel, a prototypic SOC, opened the floodgates for exploring the molecular mechanism of this pathway and its functions. This review focuses on recent advances made possible by the use of STIM and Orai as molecular tools. I will describe our current understanding of the store-operated Ca 2þ entry mechanism and its emerging roles in physiology and disease, areas of uncertainty in which further progress is needed, and recent findings that are opening new directions for research in this rapidly growing field.

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Local Ca2+ Influx through Ca2+ Release-activated Ca2+ (CRAC) Channels Stimulates Production of an Intracellular Messenger and an Intercellular Pro-inflammatory Signal

Cited by 72 publications

References 39 publications

Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

Coupling of Ca2+ Microdomains to Spatially and Temporally Distinct Cellular Responses by the Tyrosine Kinase Syk

Store-Operated Calcium Channels: New Perspectives on Mechanism and Function

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