Calreticulin: Roles in Cell-Surface Protein Expression

Jiang, Yue; Dey, Sandeepa; Matsunami, Hiroaki

doi:10.3390/membranes4030630

Cited by 32 publications

(22 citation statements)

References 53 publications

(56 reference statements)

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“…As a chaperone protein, calreticulin is also linked with HSP90. This protein is expressed on the cellular surface and its putative role in cell adhesion, migration or apoptosis has been documented 49 . In addition, calreticulin modulates integrin-dependent Ca 2+ signaling [Michalak et al, 1999] and different patterns of expression have been reported during implantation in mice [Cheng et al, 2009].…”

Section: Structural/cytoskeleton Calcium Metabolism and Membrane Promentioning

confidence: 99%

“…In addition, calreticulin modulates integrin-dependent Ca 2+ signaling [Michalak et al, 1999] and different patterns of expression have been reported during implantation in mice [Cheng et al, 2009]. This protein is expressed on the cellular surface and its putative role in cell adhesion, migration or apoptosis has been documented 49 . In addition, calreticulin modulates integrin-dependent Ca 2+ signaling 50 and different patterns of expression have been reported during implantation in mice 51 .…”

Section: Structural/cytoskeleton Calcium Metabolism and Membrane Promentioning

confidence: 99%

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Changes in protein expression profiles in bovine endometrial epithelial cells exposed to E. coli LPS challenge

et al. 2017

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Section: Structural/cytoskeleton Calcium Metabolism and Membrane Promentioning

confidence: 99%

Section: Structural/cytoskeleton Calcium Metabolism and Membrane Promentioning

confidence: 99%

Changes in protein expression profiles in bovine endometrial epithelial cells exposed to E. coli LPS challenge

et al. 2017

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“…Calreticulin (CALR) is an endoplasmic reticulum (ER)-resident protein that regulates the functions of numerous proteins by chaperoning them to their active sites in response to Ca 2+ [1,2]. Structurally and functionally, mature human CALR (residues 18-417; UniProt ID: P27797) can be divided into three domains, a globular N-terminal domain (N-domain, N-CARL, residues 18–197), an extended proline-rich P-domain (residues 198–308), and an acidic C-terminal domain (C-domain, C-CARL, residues 309–417) [3,4].…”

mentioning

confidence: 99%

The Calreticulin control of human stress erythropoiesis is impaired by JAK2V617F in polycythemia vera

Falchi

Varricchio

Martelli

et al. 2017

Experimental Hematology

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Calreticulin (CALR) is a Ca2+-binding protein that shuttles among cellular compartments with proteins bound to its N/P domains. The knowledge that activation of the human erythropoietin receptor induces Ca2+ fluxes prompted us to investigate the role of CALR in human erythropoiesis. As shown by Western blot analysis, erythroblasts generated in vitro from normal sources and JAK2V617F polycythemia vera (PV) patients expressed robust levels of CALR. However, Ca2+ regulated CALR conformation only in normal cells. Normal erythroblasts expressed mostly the N-terminal domain of CALR (N-CALR) on their cell surface (as shown by flow cytometry) and C-terminal domain (C-CALR) in their cytoplasm (as shown by confocal microscopy) and expression of both epitopes decreased with maturation. In the proerythroblast (proEry) cytoplasm, C-CALR was associated with the glucocorticoid receptor (GR), which initiated the stress response. In these cells, Ca2+ deprivation and inhibition of nuclear export increased GR nuclear localization while decreasing cytoplasmic detection of C-CALR and C-CALR/GR association and proliferation in response to the GR agonist dexamethasone (Dex). C-CALR/GR association and Dex responsiveness were instead increased by Ca2+ and erythropoietin. In contrast, JAK2V617F proErys expressed normal cell-surface levels of N-CALR but barely detectable cytoplasmic levels of C-CALR. These cells contained GR mainly in the nucleus and were Dex unresponsive. Ruxolitinib rescued cytoplasmic detection of C-CALR, C-CALR/GR association, and Dex responsiveness in JAK2V617F proErys and its effects were antagonized by nuclear export and Ca2+ flux inhibitors. These results indicates that Ca2+-induced conformational changes of CALR regulate nuclear export of GR in normal erythroblasts and that JAK2V617F deregulates this function in PV.

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“…Calreticulin is another protein located in the endoplasmatic reticulum with chaperon properties and both HSPs and calreticulin are DAMPs with pro-inflammatory abilities [58,104]. These molecules may very well be targets of aluminium ions resulting in changed conformation, modified function, and cellular re-localization.…”

Section: Cellular Stress Functionsmentioning

confidence: 99%

Aluminium Adjuvants – A Nanomaterial used as Adjuvants in Human Vaccines for Decades

Danielsson¹,

Sandberg²,

Eriksson³

2018

TOBIOTJ

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Background:Aluminium salts have been used for decades in vaccines as adjuvants to facilitate the adaptive immune response against co-administered antigens. Two types of aluminium adjuvant are mostly used, aluminium oxyhydroxide and aluminium hydroxyphosphate. Both types of aluminium adjuvant consist of nanoparticles that form loose, micrometre sized aggregates at circumneutral pH.Aluminium adjuvants constitute a well-documented example of administration of nanomaterials to humans with infrequent side effects and a safety record generally regarded as excellent. However, despite its prolonged use in human and veterinary medicine, the mechanisms behind the enhanced response and the immune stimulatory effect are still by and large unknown.Methods:The present paper reviews existing ideas regarding the immunostimulatory effects of aluminium adjuvants, with a focus on the induction of an inflammatory response by cellular stress. Reviewed information was obtained from peer-reviewed scientific papers published in 1988 to date with one exception, a paper published 1931.Results:Cellular stress causes extra cellular signalling of Danger Associated Molecular Patterns (DAMPs) and upon phagocytosis of aluminium adjuvants the cells need to manage the ingested particles.Conclusion:A persistent intracellular accumulation of aluminium adjuvants will be a solid depository of sparingly soluble aluminium salts maintaining a constant concentration of Al3+ions in the cytoplasm and this will affect multiple biochemical processes. The cell will be under constant stress and DAMP signalling will occur and we would like to suggest the maintenance of a constant concentration Al3+ions in the cytoplasm as a general underlying feature of the immune stimulation properties of aluminium adjuvants.

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Calreticulin: Roles in Cell-Surface Protein Expression

Cited by 32 publications

References 53 publications

Changes in protein expression profiles in bovine endometrial epithelial cells exposed to E. coli LPS challenge

Changes in protein expression profiles in bovine endometrial epithelial cells exposed to E. coli LPS challenge

The Calreticulin control of human stress erythropoiesis is impaired by JAK2V617F in polycythemia vera

Aluminium Adjuvants – A Nanomaterial used as Adjuvants in Human Vaccines for Decades

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