Calcium Influx Factor Is Synthesized by Yeast and Mammalian Cells Depleted of Organellar Calcium Stores (original) (raw)
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Calcium release and influx colocalize to the endoplasmic reticulum
Current Biology, 1997
Intracellular Ca 2+ is released from intracellular stores in the endoplasmic reticulum (ER) in response to the second messenger inositol (1,4,5) trisphosphate (InsP 3) [1,2]. Then, a poorly understood cellular mechanism, termed capacitative Ca 2+ entry, is activated [3,4]; this permits Ca 2+ to enter cells through Ca 2+-selective Ca 2+-release-activated ion channels [5,6] as well as through less selective store-operated channels [7]. The level of stored Ca 2+ is sensed by Ca 2+-permeant channels in the plasma membrane, but the identity of these channels, and the link between them and Ca 2+ stores, remain unknown. It has been argued that either a diffusible second messenger (Ca 2+ influx factor; CIF) [8] or a physical link [9,10] connects the ER Ca 2+-release channel and storeoperated channels; strong evidence for either mechanism is lacking, however [7,10]. Petersen and Berridge [11] showed that activation of the lysophosphatidic acid receptor in a restricted region of the oocyte membrane results in stimulation of Ca 2+ influx only in that region, and concluded that a diffusible messenger was unlikely. To investigate the relationship between ER stores and Ca 2+ influx, we used centrifugation to redistribute into specific layers the organelles inside intact Xenopus laevis oocytes, and used laser scanning confocal microscopy with the two-photon technique to 'uncage' InsP 3 while recording intracellular Ca 2+ concentration. Ca 2+ release was localized to the stratified ER layer and Ca 2+ entry to regions of the membrane directly adjacent to this layer. We conclude that Ca 2+ depletion and entry colocalize to the ER and that the mechanism linking Ca 2+ stores to Ca 2+ entry is similarly locally constrained.
Cell Calcium, 1994
Rat cerebeiiar RNA injected into Xenopus oocytes leads to the expression of putative P-type vottagedependent Ca2+ channels (VDCCS). The monitoring of intraceiiuiar Ca2' variations by recording the Ca2' dsip"dent chloride current in voltage clamped oocytes indicates that activation of these Ca + channels by depoiarization gives rise to two distinct components of cytosoiic Ca2+ elevation. if the eariy component (Tr) can be di aMbuted to the Ca2+ entry through VDCCs, the second one4(T2)ls~toa + 3 reiease from insP3 sensitive stores activated following entry. Modlficaflons of cyt* soiic Ca2+ by direct ln)ection of c$+ into oocytes or by increasing the Q?+ influx through VDCCs suggest that the Ca2' release from intraceliuiar InsPs sensitive stores can be modulated in a dffferentiai manner. Nameiy, discrete elevations of cytosoiic Ca2+ switch on the Ca2' release whereas higher Ca2+ concentrations dampen the release.
Depletion of intracellular calcium stores activates a calcium conducting …
Journal of Biological Chemistry, 1996
Receptor-mediated Ca 2+ release from inositol (1,4,5)-trisphosphate (IP 3 )-sensitive Ca 2+ stores causes "capacitative calcium entry" in many cell types (Putney, JW, Jr. (1986) Cell Calcium 7, 1-12; Putney, JW, Jr. (1990) Cell Calcium 11, 611-624). We used patch-clamp and ...
The Journal of Physiology, 2000
In rat basophilic leukaemia (RBL_1) cells, an experimental model for mucosal mast cells, calcium (Ca¥) influx is a central event in the secretion of inflammatory mediators (Ali et al. 1990; Kim et al. 1997). Activation of cell-surface receptors that couple to inositol 1,4,5-trisphosphate (IP×) production evokes a biphasic increase in intracellular Ca¥: an initial Ca¥ release phase is followed by a smaller but sustained Ca¥ influx component (Berridge, 1993). In RBL_1 cells, like other non-excitable cells, emptying of the intracellular Ca¥ stores activates a Ca¥ current called ICRAC (Ca¥ releaseactivated Ca¥ current; Hoth & Penner, 1992; Parekh & Penner, 1997). The relationship between IP×-evoked Ca¥ release and subsequent activation of ICRAC is complex. A partial dissociation between Ca¥ release and store-operated Ca¥ influx has been found in several cells including RBL_1 cells (Parekh et al. 1997; Hartmann & Verkhratsky, 1998; Liu et al. 1998). Despite its importance, the mechanisms underlying this widespread phenomenon are not known. When ICRAC is studied under conditons of physiological cytoplasmic Ca¥ buffering and IP× is used to deplete the intracellular stores, the current is not detectable, although intracellular fluorescent dyes reveal modest activation of Ca¥ influx following IP× elevation (Parekh et al. 1997; Huang et al. 1998). It is widely accepted that the stores are fully depleted under these conditions, and the inability to record any macroscopic ICRAC reflects Ca¥-dependent
The cellular and molecular basis of store-operated calcium entry
Nature Cell Biology, 2002
The impact of calcium signalling on so many areas of cell biology reflects the crucial role of calcium signals in the control of diverse cellular functions. Despite the precision with which spatial and temporal details of calcium signals have been resolved, a fundamental aspect of the generation of calcium signals -the activation of 'store-operated channels' (SOCs) -remains a molecular and mechanistic mystery. Here we review new insights into the exchange of signals between the endoplasmic reticulum (ER) and plasma membrane that result in activation of calcium entry channels mediating crucial long-term calcium signals. C alcium signals control a vast array of cellular functions ranging from short-term responses, such as contraction and secretion, to longer-term control of transcription, cell division and cell death 1,2 . In most non-excitable cells, the generation of receptor-induced cytosolic calcium signals is complex and involves two interdependent and closely coupled components: the rapid, transient release of calcium from stores in the ER and then slow and sustained entry of extracellular calcium 2-12 . Through the activation of phospholipase C (PLC) subtypes, G protein-coupled receptors and tyrosine kinase-coupled receptors generate the second messengers inositol 1,4,5-trisphosphate (InsP 3 ) and diacylglycerol (DAG). The former functions as a chemical message that diffuses rapidly within the cytosol and interacts with InsP 3 receptors (InsP 3 R) located on the ER, which function as calcium channels to release calcium stored in the ER lumen and generate the initial calcium signal phase 1,2,4 . The resulting depletion of calcium stored within the ER lumen functions as the primary trigger for a message that is returned to the plasma membrane (PM), resulting in the relatively slow activation of SOCs, which allow entry of external calcium . This sustained calcium entry phase mediates longer term cytosolic calcium signals and provides a means to replenish intracellular stores . The other product of PLC activation, DAG, also has important effects on calcium entry channels . Although the molecular identity of SOCs has not been determined, certain members of the TRP family of cation channels 19 display properties intriguingly similar to SOCs 17,18,20-23 . Two prevailing coupling scenarios to activate SOCs, involving either a diffusible chemical messenger 24-31 or physical interactions between ER and PM 5,32 , are depicted in . However, the nature of the ER-derived signal to activate SOCs remains unresolved.
The role of mitochondria in the regulation of calcium influx into Jurkat cells
European Journal of Biochemistry, 2000
In electrically nonexcitable cells the activity of the plasma membrane calcium channels is controlled by events occurring in mitochondria, as well as in the lumen of the endoplasmic reticulum. Thapsigargin, a specific inhibitor of endoplasmic reticulum Ca 2+ -ATPase, produces the release of calcium from the endoplasmic reticulum and thus, activation of store-operated calcium channels in the plasma membrane. However, thapsigargin failed to produce significant activation of the channels in Jurkat cells that had been pretreated with mitochondria-directed agents: an uncoupler (carbonyl cyanide m-chlorophenylhydrazone) and oligomycin. This is in spite of the fact that Jurkat cells pretreated with carbonyl cyanide m-chlorophenylhydrazone plus oligomycin are otherwise energetically competent, due to a high rate of glycolysis and the inhibition of mitochondrial F 1 F o -ATPase by oligomycin. The pool of intracellular ATP was found not to be influenced by the pretreatments of cells with oligomycin or with oligomycin plus carbonyl cyanide m-chlorophenylhydrazone. In the control cells, we found that the ATP pool amounted to 23.2^1.9 nmoles per 10 7 cells (n = 4). In cells pretreated with oligomycin the level of ATP was 21.8^1.9 nmoles per 10 7 cells (n = 4), and in cells pretreated with both oligomycin and an uncoupler the level of ATP was 22.1^0.2 nmoles per 10 7 cells (n = 3). Moreover, in cells pretreated with oligomycin plus carbonyl cyanide m-chlorophenylhydrazone and suspended in a nominally calcium-free medium, thapsigargin produces transient increases in cytosolic calcium identical to those in the control cells. Thus, this pretreatment does not modify either the content of intracellular calcium stores and/or the activity of calcium ATPase in the plasma membrane. Similar results were obtained when Jurkat cells were challenged by myxothiazol, a potent inhibitor of mitochondrial cytochrome bc 1 oxidoreductase. Thapsigargin, although producing calcium release from intracellular stores, was ineffective in triggering the activation of calcium channels in the plasma membrane in the case of cells pretreated with myxothiazol and oligomycin. Our results suggest that coupled mitochondria participate directly in the control of calcium channel activity in the plasma membrane of Jurkat cells. When the mitochondrial protonmotive force is collapsed, either by carbonyl cyanide m-chlorophenylhydrazone or myxothiazol, the channel remains inactive even under conditions of empty intracellular calcium stores.
1992
To study the mediation of Ca2" influx by second messengers in myeloid cells, we have combined the whole-cell patch clamp technique with microfluorimetric measurements of ICa21i,. Me2SO-differentiated HL-60 cells were loaded with the fluorescent Ca2+ indicator Indo-1, allowed to adhere to glass slides, and patch-clamped. Receptor agonists and Ca2+-ATPase inhibitors were applied by superfusion and inositol phosphates by microperfusion through the patch pipette. In voltage-clamped cells, ICa21;i elevations with a sustained phase could be induced by (a) the chemoattractant receptor agonist FMLP, (b) the Ca2+-releasing second messenger myo-inositol(1,4,5)trisphosphate IIns(1,4,5)P31, as well as its nonmetabolizable analogues, and (c) the Ca2+-ATPase inhibitor cyclopiazonic acid, which depletes intracellular Ca2+ stores. In the absence of extracellular Ca2+, responses to all stimuli were short-lasting, monophasic transients; however, subsequent addition of Ca2+ to the extracellular medium led to an immediate ICa21ji increase. In all cases, the sustained phase of the [Ca2+]i eleva-Address reprint requests to Dr.