Calreticulin Modulates Capacitative Ca2+ Influx by Controlling the Extent of Inositol 1,4,5-Trisphosphate-induced Ca2+ Store Depletion

Xu, Wen; Longo, Frank J.; Wintermantel, M. R.; Jiang, Xueying; Clark, Robert A.; Delisle, Sylvain

doi:10.1074/jbc.m002041200

Cited by 55 publications

(46 citation statements)

References 54 publications

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“…There are several reports (9,10,56,57) (11). Consistent with these studies, the decreased cellular content of calreticulin that we observed during the physiologic process of myeloid cell differentiation correlated with a commensurate decrease in the Ca 2ϩ stores.…”

Section: Fig 8 Immunoblot Analysis Of Selected Er and Cytosolic Prosupporting

confidence: 73%

“…The high Ca 2ϩ -binding capacity of calreticulin suggests that it acts as a Ca 2ϩ store or buffer within the ER, and there is evidence that in at least some cell types it is a main source of inositol 1,4,5-trisphosphate (IP 3 )-releasable Ca 2ϩ (3,5,8,9). In support of these observations, overexpression of calreticulin in some cells is accompanied by a significant increase in the Ca 2ϩ storage pool, as well as an alteration in IP 3 -mediated Ca 2ϩ release and influx (9,10). Moreover, the thapsigargin-and ionomycin-sensitive Ca 2ϩ pools were markedly reduced in calreticulin-null mouse embryonic stem cells, defects that were corrected by ectopic expression of calreticulin (11).…”

Section: Induction Of Differentiation Of Hl-60 Human Myeloid Cells Prsupporting

confidence: 64%

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Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells

Clark¹,

Li²,

Pearson³

et al. 2002

Journal of Biological Chemistry

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Induction of differentiation of HL-60 human myeloid cells profoundly affected expression of calreticulin, a Ca2؉ -binding endoplasmic reticulum chaperone. Induction with Me 2 SO or retinoic acid reduced levels of calreticulin protein by ϳ60% within 4 days. Pulse-chase studies indicated that labeled calreticulin decayed at similar rates in differentiated and undifferentiated cells (t1 ⁄2 ϳ4.6 days), but the biosynthetic rate was <10% of control after 4 days. Differentiation also induced a rapid decline in calreticulin mRNA levels (90% reduction after 1 day) without a decrease in transcript stability (t1 ⁄2 ϳ5 h). Nuclear run-on analysis demonstrated rapid downregulation of gene transcription (21% of control at 2 h). Differentiation also greatly reduced the Ca 2؉ content of the cells (25% of control), although residual Ca 2؉ pools remained sensitive to thapsigargin, ionomycin, and inositol trisphosphate. Progressive decreases were also observed in levels of calnexin and ERp57, whereas BiP/ GRP78 and protein disulfide isomerase were only modestly affected. Ultrastructural studies showed a substantial reduction in endoplasmic reticulum content of the cells. Thus, terminal differentiation of myeloid cells was associated with decreased endoplasmic reticulum content, selective reductions in molecular chaperones, and diminished intracellular Ca 2؉ stores, perhaps reflecting an endoplasmic reticulum remodeling program as a prominent feature of granulocytic differentiation.Calreticulin is a major Ca 2ϩ -binding protein present in the lumen of the endoplasmic reticulum (ER) 1 of virtually all cell types (1-3). The cDNA sequence predicts an ϳ47-kDa acidic protein with a zonal structure featuring a globular N-terminal domain, a proline-rich P domain, and a highly acidic C domain terminating in a KDEL motif, the ER retention signal (3, 4).Biophysical studies show calreticulin to be a highly asymmetric molecule consistent with this predicted three domain structure. Calreticulin binds Ca 2ϩ with both high and low affinities and with high capacity. A single high affinity site (K d ϳ1 M) is located within the P domain of the molecule and multiple low affinity sites (K d ϳ2 mM, 20 -25 mol of Ca 2ϩ /mol of protein) are present in the highly acidic C domain (3,4). The N domain contains at least one site for binding Zn 2ϩ , which appears to involve 4 of the histidine residues in this region (5, 6). Binding of these ions affects the conformation and stability of the protein (7).Numerous and apparently unrelated functions have been ascribed to calreticulin since it was first identified, but its roles in the regulation of Ca 2ϩ homeostasis and as a molecular chaperone of nascent glycoproteins are the two functions that have been most extensively characterized. Calreticulin appears to regulate intracellular Ca 2ϩ homeostasis through more than one mechanism. The high Ca 2ϩ -binding capacity of calreticulin suggests that it acts as a Ca 2ϩ store or buffer within the ER, and there is evidence that in at least some cell types it is a main so...

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Section: Fig 8 Immunoblot Analysis Of Selected Er and Cytosolic Prosupporting

confidence: 73%

Section: Induction Of Differentiation Of Hl-60 Human Myeloid Cells Prsupporting

confidence: 64%

Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells

Clark¹,

Li²,

Pearson³

et al. 2002

Journal of Biological Chemistry

Self Cite

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“…In the ER, the changes in ratio observed during physiological stimulation cover only a fraction of the full dynamic range, less than 10% [12,[15][16][17]. This limited range makes the quantification of the physiological fluctuations in [Ca 2+ ] ER very difficult.…”

Section: Design and Evolution Of Cameleonsmentioning

confidence: 99%

“…Regardless of the technique used for gene transfer, a significant time lag is required before Ca 2+ measurements can be performed. For cDNA transfection with either Ca 2+ -phosphate or cationic lipids, the measurements are typically performed between 2 and 5 days after gene transfer into the cells [9,12,[15][16][17]. Attempts to maximize the efficacy of transfection often cause a significant fraction of cells to become brightly fluorescent, with most of the fluorescence originating from irrelevant cell locations.…”

Section: Expressionmentioning

confidence: 99%

Measurements of the free luminal ER Ca 2+ concentration with targeted “cameleon” fluorescent proteins

2003

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The free ER Ca 2+ concentration, [Ca 2+ ] ER , is a key parameter that determines both the spatio-temporal pattern of Ca 2+ signals as well as the activity of ER-resident enzymes. Obtaining accurate, time-resolved measurements of the Ca 2+ activity within the ER is thus critical for our understanding of cell signaling. Such measurements, however, are particularly challenging given the highly dynamic nature of Ca 2+ signals, the complex architecture of the ER, and the difficulty of addressing probes specifically into the ER lumen. Prompted by these challenges, a number of ingenious approaches have been developed over the last years to measure ER Ca 2+ by optical means. The two main strategies used to date are Ca 2+ -sensitive synthetic dyes trapped into organelles and genetically encoded probes, based either on the photoprotein aequorin or on the green fluorescent protein (GFP). The GFP-based Ca 2+ indicators comprise the camgaroo and pericam probes based on a circularly permutated GFP, and the cameleon probes, which rely on the fluorescence resonance energy transfer (FRET) between two GFP mutants of different colors. Each approach offers unique advantages and suffers from specific drawbacks. In this review, we will discuss the advantages and pitfalls of using the genetically encoded "cameleon" Ca 2+ indicators for ER Ca 2+ measurements.

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“…calreticulin was over-expressed in HeLa cells and Xenopus oocytes (Bastianutto et al, 1995;Xu et al, 2000). Furthermore, over-expression of other known calcium storage proteins such as calsequestrin and histidine rich Ca 2þ binding protein leads to an increase in caffeine-induced Ca 2þ release (Jones et al, 1998;Sato et al, 1998;Kim et al, 2003;Fan et al, 2004;Miller et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Increased Ca²⁺ storage capacity of the skeletal muscle sarcoplasmic reticulum of transgenic mice over‐expressing membrane bound calcium binding protein junctate

Divet

Paesante

Grasso

et al. 2007

Journal Cellular Physiology

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Junctate is an integral sarco(endo)plasmic reticulum protein expressed in many tissues including heart and skeletal muscle. Because of its localization and biochemical characteristics, junctate is deemed to participate in the regulation of the intracellular Ca 2þ concentration. However, its physiological function in muscle cells has not been investigated yet. In this study we examined the effects of junctate over-expression by generating a transgenic mouse model which over-expresses junctate in skeletal muscle. Our results demonstrate that junctate over-expression induced a significant increase in SR Ca 2þ storage capacity which was paralleled by an increased 4-chloro-mcresol and caffeine-induced Ca 2þ release, whereas it did not affect SR Ca 2þ -dependent ATPase activity and SR Ca 2þ loading rates. In addition, junctate over-expression did not affect the expression levels of SR Ca 2þ binding proteins such as calsequestrin, calreticulin and sarcalumenin. These findings suggest that junctate over-expression is associated with an increase in the SR Ca 2þ storage capacity and releasable Ca 2þ content and support a physiological role for junctate in intracellular Ca 2þ homeostasis.

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Calreticulin Modulates Capacitative Ca2+ Influx by Controlling the Extent of Inositol 1,4,5-Trisphosphate-induced Ca2+ Store Depletion

Abstract: Calreticulin (CRT) is a highly conserved

Cited by 55 publications

References 54 publications

Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells

Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells

Measurements of the free luminal ER Ca 2+ concentration with targeted “cameleon” fluorescent proteins

Increased Ca²⁺ storage capacity of the skeletal muscle sarcoplasmic reticulum of transgenic mice over‐expressing membrane bound calcium binding protein junctate

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Calreticulin Modulates Capacitative Ca2+ Influx by Controlling the Extent of Inositol 1,4,5-Trisphosphate-induced Ca2+ Store Depletion

Abstract: Calreticulin (CRT) is a highly conserved

Cited by 55 publications

References 54 publications

Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells

Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells

Measurements of the free luminal ER Ca 2+ concentration with targeted “cameleon” fluorescent proteins

Increased Ca2+ storage capacity of the skeletal muscle sarcoplasmic reticulum of transgenic mice over‐expressing membrane bound calcium binding protein junctate

Contact Info

Product

Resources

About

Increased Ca²⁺ storage capacity of the skeletal muscle sarcoplasmic reticulum of transgenic mice over‐expressing membrane bound calcium binding protein junctate