Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum

Michalak, Marek; Groenendyk, Jody; Szabó, Éva; Gold, Leslie I.; Opas, Michał

doi:10.1042/bj20081847

Cited by 635 publications

(572 citation statements)

References 186 publications

Supporting

Mentioning

549

Contrasting

Unclassified

Order By: Relevance

“…All seven ER-localized chaperones and folding proteins identified are known UPR inducible proteins, suggesting the presence of ER stresses and the activation of UPR during prolonged CHO culturing. As components of the calnexin/calreticulin ER chaperone system, calreticulin and ER protein 60 (ERp60) interact and promote the proper folding of glycoproteins (Michalak et al 2009). Moreover, their roles in apoptosis have also been characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, their roles in apoptosis have also been characterized. The localization and exposure of calreticulin to cell surface during apoptosis serves as a signal for the phagocytotic engulfment of cells (Michalak et al 2009). ERp60, which folds the mitochondrial calcium-dependent neutral cysteine protease l-calpain, is responsible for the cleavage and release of membrane bound apoptosis inducing factor (AIF) into the intermembrane space of mitochondria in preparation for subsequent release into the cytosol during apoptosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

et al. 2011

View full text Add to dashboard Cite

The degradation of environmental conditions, such as nutrient depletion and accumulation of toxic waste products over time, often lead to premature apoptotic cell death in mammalian cell cultures and suboptimal protein yield. Although apoptosis has been extensively researched, the changes in the whole cell proteome during prolonged cultivation, where apoptosis is a major mode of cell death, have not been examined. To our knowledge, the work presented here is the first whole cell proteome analysis of non-induced apoptosis in mammalian cells. Flow cytometry analyses of various activated caspases demonstrated the onset of apoptosis in Chinese hamster ovary cells during prolonged cultivation was primarily through the intrinsic pathway. Differential in gel electrophoresis proteomic study comparing protein samples collected during cultivation resulted in the identification of 40 differentially expressed proteins, including four cytoskeletal proteins, ten chaperone and folding proteins, seven metabolic enzymes and seven other proteins of varied functions. The induction of seven ER chaperones and foldases is a solid indication of the onset of the unfolded protein response, which is triggered by cellular and ER stresses, many of which occur during prolonged batch cultures. In addition, the upregulation of six glycolytic enzymes and another metabolic protein emphasizes that a change in the energy metabolism likely occurred as culture conditions degraded and apoptosis advanced. By identifying the intracellular changes during cultivation, this study provides a foundation for optimizing cell line-specific cultivation processes, prolonging longevity and maximizing protein production.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Because this biological function was independent of PR3 enzymatic activity (5), it was hypothesized that it might be related to new PR3 partner protein(s) such as CRT. CRT is well-known as a calcium-binding chaperone protein mainly located in the endoplasmic reticulum, involved in calcium homoeostasis and in the folding of newly synthesized proteins (10). CRT also plays a role in many other biological systems, including functions outside the endoplasmic reticulum, indicating that the protein is a multiprocess molecule (29).…”

Section: Discussionmentioning

confidence: 99%

“…It is now commonly accepted that CRT, originally characterized as an endoplasmic reticulum chaperone protein (10), is also a majoreat-me signal expressed at the surface of apoptotic cells, including neutrophils (11). Accordingly, decreased CRT membrane expression reduced apoptotic cell uptake by phagocytes (12).…”

Section: G Ranulomatosis With Polyangiitis (Gpa) Formerly Calledmentioning

confidence: 99%

Proteinase 3, the Autoantigen in Granulomatosis with Polyangiitis, Associates with Calreticulin on Apoptotic Neutrophils, Impairs Macrophage Phagocytosis, and Promotes Inflammation

Gabillet

Millet

Pederzoli-Ribeil

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Proteinase 3 (PR3) is the target of anti-neutrophil cytoplasm Abs in granulomatosis with polyangiitis, a form of systemic vasculitis. Upon neutrophil apoptosis, PR3 is coexternalized with phosphatidylserine and impaired macrophage phagocytosis. Calreticulin (CRT), a protein involved in apoptotic cell recognition, was found to be a new PR3 partner coexpressed with PR3 on the neutrophil plasma membrane during apoptosis, but not after degranulation. The association between PR3 and CRT was demonstrated in neutrophils by confocal microscopy and coimmunoprecipitation. Evidence for a direct interaction between PR3 and the globular domain of CRT, but not with its P domain, was provided by surface plasmon resonance spectroscopy. Phagocytosis of apoptotic neutrophils from healthy donors was decreased after blocking lipoprotein receptor-related protein (LRP), a CRT receptor on macrophages. In contrast, neutrophils from patients with granulomatosis with polyangiitis expressing high membrane PR3 levels showed a lower rate of phagocytosis than those from healthy controls not affected by anti-LRP, suggesting that the LRP-CRT pathway was disturbed by PR3-CRT association. Moreover, phagocytosis of apoptotic PR3-expressing cells potentiated proinflammatory cytokine in vitro by human monocyte-derived macrophages and in vivo by resident murine peritoneal macrophages, and diverted the anti-inflammatory response triggered by the phagocytosis of apoptotic cells after LPS challenge in thioglycolate-elicited murine macrophages. Therefore, membrane PR3 expressed on apoptotic neutrophils might amplify inflammation and promote autoimmunity by affecting the anti-inflammatory “reprogramming” of macrophages.

show abstract

“…CRT is a unique endoplasmic reticulum luminal protein that participates in many cellular functions, including lectinlike chaperoning, Ca 2þ storage and signaling, regulation of gene expression, cell adhesion, wound healing, and autoimmunity (4). Many studies have shown that CRT plays an important role in regulating cell motility.…”

Section: Introductionmentioning

confidence: 99%

PTP1B Contributes to Calreticulin-Induced Metastatic Phenotypes in Esophageal Squamous Cell Carcinoma

Wang

Hao

et al. 2013

Molecular Cancer Research

View full text Add to dashboard Cite

Calreticulin (CRT) is a Ca 2þ -binding chaperone protein that alters cellular Ca 2þ -homeostasis in the endoplasmic reticulum (ER). Previously it was shown that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, the mechanisms underlying the role of CRT in esophageal carcinoma progression were investigated. Critically, depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, whereas restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knockdown of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of STAT5A, whereas knockdown of PTP1B reduced ERK1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues was strongly correlated. Importantly, PTP1B expression was associated with poor survival in patients with CRT overexpression. Overall, these data indicate a novel signaling pathway connecting CRT, STAT5A, PTP1B, and ERK1/2 in the regulation of ESCC cell migration.Implications: These findings suggest that PTP1B is a downstream effector of CRT signaling, promotes tumor progression, and can potentially be used as a new drug target for ESCC. Mol Cancer Res; 11(9); 986-94. Ó2013 AACR. IntroductionSquamous cell carcinoma is the predominant esophageal cancer occurring in the Chinese population and is correlated with a poor prognosis and a 5-year survival rate of 15% to 25% (1). One reason for the poor prognosis is that esophageal squamous cell carcinoma (ESCC) already exhibits extensive local invasion and distant metastasis at the time of initial diagnosis (2). Therefore, having a better understanding of the molecular pathogenesis of ESCC is important for early diagnosis and effective treatment of the disease.The metastatic process consists of a number of distinct steps. Tumor invasion and migration are parts of these sequential steps. A multitude of molecular changes in tumor cells could enable these cells to acquire highly motile properties that overcome cell-cell contacts and cell-extracellular matrix barriers. In a previous study, we showed that one of such molecular alterations is the overexpression of calreticulin (CRT) in ESCCs (3).

show abstract

Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum

Cited by 635 publications

References 186 publications

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

Proteinase 3, the Autoantigen in Granulomatosis with Polyangiitis, Associates with Calreticulin on Apoptotic Neutrophils, Impairs Macrophage Phagocytosis, and Promotes Inflammation

PTP1B Contributes to Calreticulin-Induced Metastatic Phenotypes in Esophageal Squamous Cell Carcinoma

Contact Info

Product

Resources

About