The conformation of calreticulin is influenced by the endoplasmic reticulum lumenal environment

Corbett, Elaine F.; Michalak, Karolina M.; Oikawa, Kimio; Johnson, Steven; Campbell, Iain D.; Eggleton, Paul; Kay, Cyril M.; Michalak, Marek

doi:10.1074/jbc.m002049200

Cited by 60 publications

(73 citation statements)

References 68 publications

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“…It is well known that arsenite provokes ER stress that leads to down-regulation of Ca 2ϩ signaling, resulting in apoptosis (41). Certainly the perturbation of Ca 2ϩ homeostasis plays a role in CRT trafficking to the cell membrane, most probably associated with the conformation that CRT adopts outside the ER (42,43). However, in the present paper we observe no differences in Ca 2ϩ homeostatic mechanism in ATE1 Ϫ/Ϫ cells compared with WT cells (Fig.…”

Section: Discussioncontrasting

confidence: 54%

Arginylated Calreticulin at Plasma Membrane Increases Susceptibility of Cells to Apoptosis

Sambrooks¹,

Carpio²,

Hallak

2012

Journal of Biological Chemistry

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Background: Calreticulin retrotranslocated from the endoplasmic reticulum to the cytoplasm is post-translationally arginylated associates to stress granules following stress that decrease Ca 2ϩ . Results: Arginylated calreticulin reaches the plasma membrane as a response to stress. Conclusion: Arginylation confers to calreticulin a function as one of the preapoptotic signals of the cells. Significance: Arginylated calreticulin is a novel factor involved in stress-induced apoptosis.

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Section: Discussioncontrasting

confidence: 54%

Arginylated Calreticulin at Plasma Membrane Increases Susceptibility of Cells to Apoptosis

Sambrooks¹,

Carpio²,

Hallak

2012

Journal of Biological Chemistry

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“…Implications of the C domain sequence and length variations might also lie in its sensitivity to proteolytic activity. Earlier reports have shown that the C domain is sensitive to degradation, which might affect the subcellular location and functionality of CRTs (Corbett et al, 2000;Persson et al, 2002a). Therefore, the differences observed in the domain could affect both the stability of the protein, possibly functioning as a turnover mechanism, or as a switch for other subcellular localizations and interacting components of CRTs.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Analyses and Expression Studies Reveal Two Distinct Groups of Calreticulin Isoforms in Higher Plants

et al. 2003

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Calreticulin (CRT) is a multifunctional protein mainly localized to the endoplasmic reticulum in eukaryotic cells. Here, we present the first analysis, to our knowledge, of evolutionary diversity and expression profiling among different plant CRT isoforms. Phylogenetic studies and expression analysis show that higher plants contain two distinct groups of CRTs: a CRT1/CRT2 group and a CRT3 group. To corroborate the existence of these isoform groups, we cloned a putative CRT3 ortholog from Brassica rapa. The CRT3 gene appears to be most closely related to the ancestral CRT gene in higher plants. Distinct tissue-dependent expression patterns and stress-related regulation were observed for the isoform groups. Furthermore, analysis of posttranslational modifications revealed differences in the glycosylation status among members within the CRT1/CRT2 isoform group. Based on evolutionary relationship, a new nomenclature for plant CRTs is suggested. The presence of two distinct CRT isoform groups, with distinct expression patterns and posttranslational modifications, supports functional specificity among plant CRTs and could account for the multiple functional roles assigned to CRTs.Calreticulin (CRT) is a highly conserved protein mainly localized to the endoplasmic reticulum (ER) in plants and to the ER/sarcoplasmic reticulum in mammals (for review, see Crofts and Denecke, 1998;Michalak et al., 1999;Hadlington and Denecke, 2000;Johnson et al., 2001). CRT is a multifunctional protein, suggested to be involved in over 40 intra-and extracellular processes in mammalian cells. However, the main focus has been on its role in calcium signaling (Camacho and Lechleiter, 1995;Nakamura et al., 2001;Arnaudeau et al., 2002) and as a chaperone (Hebert et al., 1996;Saito et al., 1999;Nakamura et al., 2001). CRT comprises three major subdomains: a highly conserved N domain, a high-affinity but low-capacity Ca 2ϩ -binding P domain, and a lowaffinity but high-capacity Ca 2ϩ -binding C domain ending with an ER retention signal (Michalak et al., 1999).Although the role of CRTs as chaperone-like proteins and in calcium signaling is well established in mammals, the functions of CRT have been elusive in plants until recently. Plant CRTs have been shown to bind calcium with similar characteristics as their mammalian homologs (Chen et al., 1994;Hassan et al., 1995;Navazio et al., 1995;Coughlan et al., 1997;Li and Komatsu, 2000) and recently also to have calcium-storing functions in the ER of plant cells (Persson et al., 2001;Wyatt et al., 2002). In contrast to most animal CRTs, glycosylation of CRTs is generally observed in plants (Navazio et al., 1995(Navazio et al., , 2002Pagny et al., 2000). Plant CRTs are up-regulated in response to a variety of stress-mediated stimuli, e.g. pathogenrelated signaling molecules (Denecke et al., 1995;Jaubert et al., 2002) and gravistimulation (Heilmann et al., 2001), and are highly expressed during mitosis (Denecke et al., 1995), embryogenesis (Borisjuk et al., 1998), and in floral tissues (Chen et al., 1994;...

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“…protein disulphide-isomerase and ERp57, inactive [9]. However, these principles of Ca 2+ -dependent protein folding have been assessed mainly on recombinant proteins [7,8,10] or by artificially applying excessive ER stress [11][12][13], while a detailed analysis of its kinetics and correlation with physiological Ca 2+ fluctuations are lacking. While there are studies that address this issue [14], it still remains questionable whether the ER protein-folding machinery is influenced by spatial and temporal dynamics of [Ca 2+ ] ER in intact cells and, if so, how efficient protein folding is maintained under physiological cell stimulation.…”

Section: Introductionmentioning

confidence: 99%

“…Initially characterized as Ca 2+ -binding protein of the sarcoplasmic reticulum [6], conformation [7], chaperone interactions [8] and thus activity of calreticulin have been shown to be directly affected by [Ca 2+ ] ER (free ER Ca 2+ concentration). A decrease in ambient [Ca 2+ ] renders the calreticulin cycle and associated folding catalysts, i.e.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum

Osibow

Frank

Malli

et al. 2006

Biochemical Journal

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Considering the physiological Ca 2+ dynamics within the ER (endoplasmic reticulum), it remains unclear how efficient protein folding is maintained in living cells. Thus, utilizing the strictly folding-dependent activity and secretion of LPL (lipoprotein lipase), we evaluated the impact of ER Ca 2+ content and mitochondrial contribution to Ca 2+ -dependent protein folding. Exhaustive ER Ca 2+ depletion by inhibition of sarcoplasmic/ endoplasmic reticulum Ca 2+ -ATPases caused strong, but reversible, reduction of cell-associated and released activity of constitutive and adenovirus-encoded human LPL in CHO-K1 (Chinesehamster ovary K1) and endothelial cells respectively, which was not due to decline of mRNA or intracellular protein levels. In contrast, stimulation with the IP 3 (inositol 1,4,5-trisphosphate)-generating agonist histamine only moderately and transiently affected LPL maturation in endothelial cells that paralleled a basically preserved ER Ca 2+ content. However, in the absence of extracellular Ca 2+ or upon prevention of transmitochondrial Ca 2+ flux, LPL maturation discontinued upon histamine stimulation. Collectively, these data indicate that Ca 2+ -dependent protein folding in the ER is predominantly controlled by intraluminal Ca 2+ and is largely maintained during physiological cell stimulation owing to efficient ER Ca 2+ refilling. Since Ca 2+ entry and mitochondrial Ca 2+ homoeostasis are crucial for continuous Ca 2+ -dependent protein maturation in the ER, their pathological alterations may result in dysfunctional protein folding.

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The conformation of calreticulin is influenced by the endoplasmic reticulum lumenal environment

Cited by 60 publications

References 68 publications

Arginylated Calreticulin at Plasma Membrane Increases Susceptibility of Cells to Apoptosis

Arginylated Calreticulin at Plasma Membrane Increases Susceptibility of Cells to Apoptosis

Phylogenetic Analyses and Expression Studies Reveal Two Distinct Groups of Calreticulin Isoforms in Higher Plants

Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum

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