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Calnexin and Calreticulin, ER Associated Modulators of Calcium Transport in the ER

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Calreticulin (CRT) and calnexin (CNX) are members of a family of endoplasmic reticulum (ER) chaperones that fold newly synthesized polypeptides. Aside from their role as foldases in the ER, our laboratory has shown that all members of this family of proteins modulate Ca2+ oscillations. In Xenopus oocytes and other cells, stimulation by G-protein and tyrosine coupled receptors results in Ca2+ release from the Inositol 1,4,5 trisphosphate receptor (IP3R) located in the ER. Following release, Ca2+ is re-sequestered into the ER by Ca2+ ATPases of the SERCA family. CRT and CNX overexpression inhibit Ca2+ oscillations when co-expressed with SERCA2b or when oocytes are treated with pyruvate malate to induce oscillations. By domain deletion mutagenesis of CRT we have determined that the N and P domains are necessary for the inhibition of Ca2+ oscillations. The mechanism of inhibition may involve a lectin-like interaction since mutagenesis of a lumenal asparagine to alanine in SERCA2b destroys the inhibitory effect. Coexpression of SERCA2a (which lacks the luminal asparagine) with either CRT or CNX does not inhibit Ca2+ oscillations, consistent with the notion that a lectin interaction may be involved. Unlike CRT, which is entirely lumenal, CNX has a cytosolic domain that is phosphorylated by multiple kinases. Mutagenesis of two PKC/PDK residues in CNX indicated that S562 supports phosphorylation. Expression of SERCA2b with a mutated CNX in S562 prevents the inhibition of Ca2+ oscillations suggesting that this residue serves as a phosphorylatable regulatory switch controlling the interaction of CNX with SERCA2b. Indeed, immunoprecipitations with a CNX specific antibody of oocytes treated with or without IP3 and preloaded with [γ-32P]-ATP demonstrated that S562 is phosphorylated at rest and dephosphorylated in response to IP3. Phosphorylation-mediated control of the interaction of CNX with SERCA2b is of significance since it suggests a bi-directional mode of communication between the Ca2+ signaling system and the folding machinery in the ER to maintain Ca2+ homeostasis in the organelle. The maintenance of Ca2+ homeostasis in the ER is then essential for protein folding.


In the past six years the goal of our laboratory has been to understand the role of ER chaperone proteins in regulating Ca2+ signaling. Our studies have primarily focused on Ca2+ re-uptake into the ER lumen by the family of sarco-endoplasmic reticulum Ca2+ ATPases (SERCAs). Prior to our work, SERCAs were largely perceived as housekeeping enzymes, with very little dynamic regulation. In addition, ER chaperone proteins were largely thought to be involved only in nascent protein folding. We discovered that at least two ER chaperone proteins, CRT and CNX, can modulate Ca2+ ATPase activity. This regulation occurs with ER resident mature proteins such as SERCA2b and is consistent with the need to maintain ER Ca2+ concentrations at levels that are optimal for protein folding. These findings underscore the necessity to expand our classical views of Ca2+ signaling and ER chaperones. In this chapter, we review the evidence that has lead to this new model of ER Ca2+ signaling.

Our initial studies arose from the observations that increments in the state of Ca2+ store refilling correlated with the sensitivity of the inositol 1,4,5 trisphosphate receptor (IP3R) to release Ca2+.1 These reports suggested that the luminal Ca2+ concentration could regulate Ca2+ release. To investigate this problem, we chose to manipulate ER luminal Ca2+ concentrations by overexpressing calreticulin (CRT), a prototypical Ca2+ storage protein2 that is expressed at millimolar concentrations in the ER.3,4 Our hypothesis was simply that higher Ca2+ levels in the lumen of the ER would increase Ca2+ oscillations via the IP3R (to increase release) or via SERCA (to increase uptake). As presented below, we successfully determined that IP3 induced Ca2+ release could in fact be regulated by altering the expression levels of CRT. In addition, overexpression of CNX, a closely related, but membrane anchored family member of CRT also regulated Ca2+ release. However, our approach also led to several unexpected findings that changed our understanding of the underlying physiology. Namely, that high capacity Ca2+ storage in CRT was not responsible for the effects observed, as discussed later. Before we discuss these data, we briefly review our experimental system.

Xenopus Oocytes As an Expression System

Xenopus oocytes were used throughout these studies. A complete description of this system is available.5 Briefly, we used IP3-induced Ca2+ wave activity to assay both Ca2+ release and Ca2+ uptake. The rising phase of individual waves reflects the activity of the IP3Rs and the decay phase reflects the uptake processes contributed mainly by Ca2+ ATPases of the SERCA family. Mitochondria can also contribute to the decay phase in the presence of energizing respiratory chain substrates.6 Cytosolic Ca2+ is imaged with Ca2+ indicator dyes and confocal microscopy. The advantage of this approach is that all experimental measurements can be carried out in vivo. The disadvantage is that contributions to the Ca2+ signal from Ca2+ release vs Ca2+ uptake cannot be precisely distinguished. Consequently, the functional Ca2+ oscillations assay is complemented by molecular and biochemical techniques.

Calreticulin and Calnexin Have an Inhibitory Effect on Ca2+ Oscillations

Overexpression of CRT7 or CNX8 in oocytes reduces the number of oocytes displaying IP3-mediated Ca2+ oscillations. In the remaining oocytes that exhibit repetitive activity, the amplitude and frequency of Ca2+ oscillations was significantly lower.7,9 These observations were consistent with an effect of CRT or CNX on the endogenous SERCA pump to inhibit uptake or on the IP3R to favor Ca2+ release. We decided to test the “SERCA” hypothesis first and this is what we have focused in this chapter. We had previously reported that overexpression of SERCA pumps leads to an increase in the frequency of Ca2+ oscillations.10 To determine whether the inhibitory effect of CRT and CNX on Ca2+ oscillations was due to inhibition of pump activity, we co-expressed CRT7,9 and CNX8 with SERCA2b, the ubiquitous Ca2+ ATPase of the ER. In this high background of Ca2+ oscillations, CRT still had a strong inhibitory effect. There was a significant decrease in the number of oocytes displaying Ca2+ oscillations, and in those oocytes that had repetitive Ca2+ release, there was a decrease in period between waves and a corresponding decrease in the decay time of individual oscillations (measured as the 50% decrease in T1/2).8,9 Energization of mitochondria by respiratory substrates (pyruvate-malate, PM) also modulates cytosolic Ca2+ by eliciting robust, low-frequency synchronized Ca2+ oscillations.6 In yet another control experiement, we demonstrated that overexpression of either CRT7 or CNX 8 in oocytes treated with PM also reduces the number of oocytes that have Ca2+ oscillations and lowered the amplitude and frequency of oscillations in those oocytes that still had repetitive activity. We concluded from these experiments that the most parsimonious explanation of the data was that Ca2+ oscillations were decreased by an inhibition of endogenous SERCA2b.7,8 Furthermore, since both CRT and CNX have only the conserved P-domain in common, inhibition of Ca2+ oscillations was likely being mediated by a lectin or chaperone interaction with the SERCA substrate as discussed below.

The observed inhibitory effects of CRT and CNX may be due to a physical interaction with the pump. Both chaperones contribute to the folding and oligomerization of glycoproteins in the ER.1114 The lectin domain was thought to be in the central portion of the P-domain.15 However more recently it is the N domain that is considered to contain the lectin binding domain.16 In CRT, this domain has a low affinity Ca2+ binding site and is responsible for binding to the substrate during protein folding. Recent evidence suggests that the P-domain is flexible and is responsible for binding to the thioreductase ERp57, which together with CRT and CNX forms inter or intra disulfide bonds with the substrate.1619 The Ca2+ storage domain is in the C-domain of CRT.2 We performed domain deletion mutagenesis of CRT to determine whether the inhibition of Ca2+ oscillations was due to Ca2+ storage or lectin interaction with SERCA2b, which has a consensus site for glycosylation on the 11th transmembrane segment. Mutant ΔC contains the N+P domains, but lacks the C domain. Similarly, the ΔP mutant has the N+C domain and lacks the P-domain, while the ΔPC mutant only carries the N-domain. All mutants were made with a KDEL ER retention signal and we confirmed their localization to the ER by confocal immunofluorescence.7 We found that inhibition of Ca2+ oscillations in CRT overexpressing oocytes requires the N+P domain.7 Our initial bias had been that overexpression of CRT would increase the amount of releasable Ca2+ from the ER by working as a Ca2+ storage protein. However, deletion of the C-domain did not remove the inhibitory action of CRT on Ca2+ oscillations, clearing demonstrating that the Ca2+ storage properties of CRT were not responsible for our observed effects. Rather, we thought that the inhibitory activity of CRT on Ca2+ oscillations may be mediated by a lectin-like interaction between CRT and the pump since the N+P domains are required. This model is also consistent with the inhibitory effect of CNX on Ca2+ oscillations as discussed further below.

Inhibition of Ca2+ Oscillations Is Mediated by the COOH Terminus of SERCA2b

The SERCA2 gene generates two alternative spliced products that are expressed in a tissue and developmental specific manner.2024 SERCA2a, the heart isoform24 is shorter having only the prototypical 10 transmembrane (TM) segments. SERCA2b is ubiquitously expressed 24 and deviates structurally from other Ca2+ ATPases by having an 11th TM segment. The COOH terminus of SERCA terminates in the ER lumen with a glycosylation consensus signal at asparagine N1036 25. To test the hypothesis that glycosylation was required for pump inhibition, we first performed experiments in which SERCA2a or SERCA2b were co-expressed with CRT.9 Our prediction was that CRT would interact with the COOH terminus of SERCA2b causing inhibition of Ca2+ oscillations whereas oscillations should not be affected by co-expression of the CRT with SERCA2a, which only has 10 TM segments. Indeed this was the case. Ca2+ oscillations were similar in all respects regardless of whether the oocytes overexpressed either SERCA2a alone or SERCA2a + CRT.9 On the other hand Ca2+ oscillations were inhibited when SERCA2b was expressed with CRT.7,9 This critical finding suggested that a direct interaction between CRT and the COOH terminus of SERCA2b was responsible for the luminal modulation of the pump. To test this hypothesis further, we created a site directed mutant of SERCA2b (SERCA2b-N1036A) in which the asparagine was mutated to alanine. Two groups of oocytes were overexpressed, those coexpressing SERCA2b-N1036A + ΔC mutant and oocytes expressing SERCA2b-N1036A alone.9 We found that N1036 was absolutely required for the inhibitory effect of CRT. These results, together with the findings from the another group of investigators demonstrate that progressive deletion of the COOH terminus of SERCA2b converts SERCA2b to a SERCA2a22,23 suggest that the COOH terminus of SERCA2b is critical in determining the differences between the two SERCA2 Ca2+ ATPases. Furthermore the findings suggest that an interaction of CRT and CNX at the COOH terminus of SERCA2b may require N1036 glycosylation.

Interaction of CNX with the COOH Terminus of SERCA2b

CNX behaves similarly to CRT in the control of Ca2+ oscillations.8 Since it has a similar P-like domain in the lumen, but no Ca2+ binding domain there, the inhibition of Ca2+ oscillations is consistent with a glycosylation mediated effect. To test this hypothesis, we determined first whether SERCA2b was indeed glycosylated. We generated constructs for expression of the TM9 to TM11 of SERCA2b (SERCA2b/TM9-11) as well as the equivalent mutant with the 1036A mutation. In addition, we generated a SERCA2a/TM9-10 mutant. Correct polytopic insertion in the ER membrane of similar constructs was previously demonstrated.25 We performed in vitro translations in rabbit reticulosite lysate in the presence of canine pancreatic microsomes. All constructs ran at the predicted molecular mass (SERCA2b and SERCA2b-N1036A/TM9-11, ˜13.2 kD; and SERCA2a ˜7.2 kD). When run on SDS-PAGE, we observed no migrational difference between SERCAb/TM9-11 and SERCA2b-N1036/ TM9-11, despite the fact that a positive control, S. cerevisiae α factor displayed full glycosylation at three sites.8 This indicated that N1036 was not glycosylated. To corroborate this finding, we treated In vitro translated products SERCAb/TM9-11 and SERCA2b-N1036/TM9-11 with endoglycosidase H (endo H). Addition of EndoH did not alter the mobility shift of SERCAb/ TM9-11 and SERCA2b-N1036/TM9-11 despite the fact that the enzyme caused a complete downward shift of positive control S. cerevisiae α factor, which is glycosylated in three asparagines.8 This finding may not yet rule out glycosylation at this N1036 and more sophisticated analysis is required to conclusively demonstrate glycosylation. Further more rigorous analysis needs to be completed to demonstrate whether SERCA2b is glycosylated at N1036. Irrespective of the state of glycosylation of N1036, it is still possible that CNX engages the SERCA2b substrate via a peptide-peptide interaction. Indeed, both CRT and CNX are known to bind to substrates via peptide-peptide interactions as traditional chaperones do.26,27 To determine if an interaction existed between CNX and the COOH tail of SERCA2b, endogenous CNX from the microsomes were immunoprecipitated by a CNX-specific antibody from the in vitro translated products of SERCA2a/TM9-10 or SERCA2b/TM9-11. Co-immunoprecipitated proteins were subsequently detected by fluorography. We demonstrated an interaction of CNX with SERCA2b, a very reduced interaction with SERCA2b-N1036A and as expected, no interaction with SERCA2a.8 Furthermore, the controls behaved as expected, i.e., S. cerevisiae α factor was shown to interact with CNX and the negative control (no mRNA supplemented in the in vitro translation reaction) did not show an interaction. Together, these results suggest that there is a specific interaction involving CNX and SERCA 2b but not with SERCA2a. Further, this interaction is localized at the COOH tail of SERCA2b. These observations combined with our imaging data suggest that the differences between SERCA2a and SERCA2b are due to an interaction of CNX with the COOH terminus of SERCA2b and strengthen our view that the inhibition of Ca2+ oscillations is dependent on this interaction.

A PKC Phosphorylation Site in CNX Regulates Inhibition of Ca2+ Oscillations

CNX is a Type I, single pass transmembrane segment protein with multiple phosphorylation sites in the cytosol. These sites fit the consensus sequences for protein kinase C (PKC/PDK) and casein kinase 2 (CK2).28,29 The PKC sites provided the attractive possibility that activation of the IP3R signaling system could directly regulate their phosphorylation by activating a Ca2+ sensitive PKC. The PKC/PDK sites would then serve as a regulatory switch in the control of Ca2+ oscillations or in the control of glycoprotein binding to substrates in the ER. Our strategy to test this hypothesis was to mutate the phosphorylation sites and overexpress the constructs in oocytes. Two PKC/PDK sites are present in CNX, S562 and S485. Mutations to alanine were made singly and at both sites. When co-expressed with SERCA2b, we found that the COOH terminal mutant (CNX-S562) did not inhibit Ca2+ oscillations. This result indicated that phosphorylation controlled the interaction of CNX with the pump and supported our model that phosphorylation of this site behaved as a regulatory switch controlling Ca2+ oscillations.8 To corroborate this point, a cytosolic peptide spanning the S562 site was generated (CNXcyt) to compete with the endogenous kinase controlling the inhibition of Ca2+ oscillations. When this peptide was co-expressed with SERCA2b and CNX, it prevented the inhibition of Ca2+ oscillations, suggesting that it was efficiently acting as a pseudosubstrate for the endogenous kinase that otherwise was responsible for phosphorylating the PKC/PDK sites.8 The identity of this kinase appears to be PDK.29

We determined the state of phosphorylation of CNX at rest and under conditions of IP3-mediated mobilization of Ca2+. CNX + SERCA2b or CNX-S562A mutant + SERCA2b, or CNX + SERCA2b + CNXcyt. were overexpressed in oocytes. We prelabelled oocytes with [γ32P]ATP and injected them with either water (control) or IP3 (300 nM final) to mobilize Ca2+ from intracellular stores. CNX was then immunoprecipitated with a specific antibody and found to be phosphorylated at rest and dephosphorylated by IP3 Ca2+ release.8 Importantly, immunoprecipitation of CNX from oocytes overexpressing CNX-S562A mutant + SERCA2b showed that CNX was minimally phosphorylated at rest and this level of phosphorylation was not changed by mutagenesis, suggesting that S562 supports phosphorylation and it is dephosphorylated by a Ca2+ dependent phosphatase.8 Ongoing work in our laboratory has indicated that the identity of this phosphatase is calcineurin (CN), which was initially recognized as Ca2+ dependent by Klee and co-workers.30 These data suggest that CN dephosphorylates CNX and that this dephosphorylation controls the dissociation of CNX with SERCA2b.

The studies described here have focused on the “SERCA” hypothesis. Based on our data, CRT (unpublished data) and CNX8 are associated with SERCA2b and inhibit its activity when Ca2+ stores are full (i.e., under resting conditions). In this state, the pump is sufficiently active to maintain the ER lumen at full Ca2+ capacity. This environment is optimal for protein folding given the requirement of ER chaperone activity for Ca2+.31 When the IP3 signaling pathway is activated several rapid changes occur. First, IP3-mediated Ca2+ release depletes Ca2+ from the ER with a corresponding mirror image increase in the cytosol. These cytosolic increases cause activation of the Ca2+ dependent phosphatase CN, which de-phosphorylates CNX. This results in the dissociation of CNX from SERCA2b, removing pump inhibition. The return to maximum pumping activity rapidly refills the ER lumen and minimizes the potential risk of impaired protein folding during cytosolic Ca2+ signaling. In our view, the role of CRT/CNX regulation of SERCA2b activity is to minimize the duration of ER Ca2+ depletion (see Fig. 1).

Figure 1. Model of CRT/CNX regulation of ER Ca2+ signaling.

Figure 1

Model of CRT/CNX regulation of ER Ca2+ signaling. Adapted from Roderick et al 2001.


Missiaen L, Taylor CW, Berridge MJ. Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes. J Physiol. 1992;455:623–40. [PMC free article: PMC1175662] [PubMed: 1484365]
Baksh S, Michalak M. Expression of calreticulin in Escherichia coli and identification of its Ca2+binding domains. J Biol Chem. 1991;266:21458–65. [PubMed: 1939178]
Fliegel L, Burns K, MacLennan DH. et al. Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1989;264(36):21522–8. [PubMed: 2600080]
Milner RE, Baksh S, Shemanko C. et al. Calreticulin, and not calsequestrin, is the major calcium binding protein of smooth muscle sarcoplasmic reticulum and liver endoplasmic reticulum. J Biol Chem. 1991;266(11):7155–65. [PubMed: 2016321]
Camacho P, Lechleiter JD. Xenpus oocytes as a tool in calcium signaling researchIn: Putney J, ed.Calcium Signaling Boca Raton: CRC Press,2000157–81.
Jouaville LS, Ichas F, Holmuhamedov EL. et al. Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes. Nature. 1995;377(6548):438–41. [PubMed: 7566122]
Camacho P, Lechleiter JD. Calreticulin inhibits repetitive intracellular Ca2+ waves. Cell. 1995;82(5):765–71. [PubMed: 7671304]
Roderick HL, Lechleiter JD, Camacho P. Cytosolic phosphorylation of calnexin controls intracellular Ca(2+) oscillations via an interaction with SERCA2b. J Cell Biol. 2000;149(6):1235–48. [PMC free article: PMC2175122] [PubMed: 10851021]
John LM, Lechleiter JD, Camacho P. Differential modulation of SERCA2 isoforms by calreticulin. J Cell Biol. 1998;142(4):963–73. [PMC free article: PMC2132884] [PubMed: 9722609]
Camacho P, Lechleiter JD. Increased frequency of calcium waves in Xenopus laevis oocytes that express a calcium-ATPase. Science. 1993;260(5105):226–9. [PubMed: 8385800]
Bergeron JJ, Brenner MB, Thomas DY. et al. Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. Trends Biochem Sci. 1994;19(3):124–8. [PubMed: 8203019]
Ellgaard L, Helenius A. ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol. 2001;13(4):431–7. [PubMed: 11454449]
Jakob CA, Chevet E, Thomas DY. et al. Lectins of the ER quality control machinery. Results Probl Cell Differ. 2001;33:1–17. [PubMed: 11190669]
Helenius A, Trombetta ES, Hebert DN. et al. Calnexin, Calreticulin, and the folding of glycoproteins. Trends Cell Biol. 1997;7:193–200. [PubMed: 17708944]
Michalak M, Milner RE, Burns K. et al. Calreticulin. Biochem J. 1992;285(Pt 3):681–92. [PMC free article: PMC1132847] [PubMed: 1497605]
Schrag JD, Bergeron JJ, Li Y. et al. The Structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol Cell. 2001;8(3):633–44. [PubMed: 11583625]
Ellgaard L, Riek R, Herrmann T. et al. NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA. 2001;98(6):3133–8. [PMC free article: PMC30619] [PubMed: 11248044]
Ellgaard L, Riek R, Braun D. et al. Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment. FEBS Letters. 2001;488(1-2):69–73. [PubMed: 11163798]
Frickel EM, Riek R, Jelesarov I. et al. TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain. Proc Natl Acad Sci USA. 2002;99(4):1954–9. [PMC free article: PMC122301] [PubMed: 11842220]
Gunteski-Hamblin AM, Greeb J, Shull GE. A novel Ca2+ pump expressed in brain, kidney, and stomach is encoded by an alternative transcript of the slow-twitch muscle sarcoplasmic reticulum Ca-ATPase gene. Identification of cDNAs encoding Ca2+ and other cation-transporting ATPases using an oligonucleotide probe derived from the ATP-binding site. J Biol Chem. 1988;263(29):15032–40. [PubMed: 2844797]
Lytton J, Westlin M, Burk SE. et al. Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. J Biol Chem. 1992;267(20):14483–9. [PubMed: 1385815]
Verboomen H, Wuytack F, De Smedt H. et al. Functional difference between SERCA2a and SERCA2b Ca2+ pumps and their modulation by phospholamban. Biochem J. 1992;286(Pt 2):591–5. [PMC free article: PMC1132938] [PubMed: 1326945]
Verboomen H, Wuytack F, Van den Bosch L. et al. The functional importance of the extreme C-terminal tail in the gene 2 organellar Ca(2+)-transport ATPase (SERCA2a/b). Biochem J. 1994;303(Pt 3):979–84. [PMC free article: PMC1137642] [PubMed: 7980471]
Wu KD, Lee WS, Wey J. et al. Localization and quantification of endoplasmic reticulum Ca(2+)-ATPase isoform transcripts. Am J Physiol. 1995;269(3Pt 1):C775–84. [PubMed: 7573409]
Bayle D, Weeks D, Sachs G. The membrane topology of the rat sarcoplasmic and endoplasmic reticulum calcium ATPases by in vitro translation scanning. J Bio Chem. 1995;270(43):25678–84. [PubMed: 7592746]
Ihara Y, Cohen-Doyle MF, Saito Y. et al. Calnexin discriminates between protein conformational states and functions as a molecular chaperone in vitro. Mol Cell. 1999;4(3):331–41. [PubMed: 10518214]
Saito Y, Ihara Y, Leach MR. et al. Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins. EMBO J. 1999;18(23):6718–29. [PMC free article: PMC1171734] [PubMed: 10581245]
Tjoelker LW, Seyfried CE, Eddy RL Jr. et al. Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5. Biochemistry. 1994;33(11):3229–36. [PubMed: 8136357]
Wong HN, Ward MA, Bell AW. et al. Conserved in vivo phosphorylation of calnexin at casein kinase II sites as well as a protein kinase C/proline-directed kinase site. J Biol Chem. 1998;273(27):17227–35. [PubMed: 9642293]
Klee CB, Ren H, Wang X. Regulation of the calmodulin-stimulated protein phosphatase, calcineurin. J Biol Chem. 1998;273(22):13367–70. [PubMed: 9593662]
Corbett EF, Oikawa K, Francois P. et al. Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J Biol Chem. 1999;274(10):6203–11. [PubMed: 10037706]
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