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Calreticulin Regulates Syncytialization Through Control of the Synthesis and Transportation of E-Cadherin in BeWo Cells.

Endocrinology | 2019

During placental development, mononuclear cytotrophoblasts differentiate and fuse to syncytiotrophoblasts (STBs) to form syncytia, which secrete human chorionic gonadotropin (hCG). Decreased maternal perfusion of the placenta, which leads to placental dysfunction, induces changes in trophoblast syncytialization. Our previous study showed that calreticulin (CRT), a Ca2+-binding molecular chaperone found in the endoplasmic reticulum, is expressed in the human placenta and is involved in regulating extravillous trophoblast invasion, although its role in villous trophoblasts remains unclear. In this study, we investigated the functional role of CRT in trophoblast differentiation using the human trophoblast-like cell line BeWo, in which CRT gene expression was knocked down. We found that CRT was highly expressed in human third-trimester placentas and mainly localized in STBs. The fetal growth restriction group exhibited significantly lower CRT expression levels than did the control group. In BeWo cells, CRT knockdown markedly suppressed forskolin-induced cell fusion and β-hCG secretion. As for the mechanism responsible for these effects, the cell surface expression of E-cadherin, a key adhesion molecule related to syncytialization, was decreased, and E-cadherin accumulated adjacent to the Golgi apparatus in the CRT-knockdown cells, which led to dysfunctional cell-to-cell adhesion. Additionally, metabolic labeling and a pulse-chase study revealed that the protein expression of E-cadherin was suppressed at the translational level in the CRT-knockdown cells. Collectively, these results demonstrate that CRT regulates syncytialization by ensuring appropriate control of both the synthesis and transportation of E-cadherin, suggesting that CRT expression is important for placental development during pregnancy.

Pubmed ID: 30551188 RIS Download

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GM130 antibody [EP892Y] (antibody)

RRID:AB_880266

This monoclonal targets GM130 antibody [EP892Y]

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ERp57, pAb (antibody)

RRID:AB_10616507

This polyclonal targets ERp57 pAb

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Cytokeratin 7 (antibody)

RRID:AB_2134589

This monoclonal targets OTN 11, ovarian carcinoma cell line (1, 8).

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Purified Mouse Anti-E-cadherin (antibody)

RRID:AB_397580

This monoclonal targets E-cadherin

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Mouse (G3A1) mAb IgG1 Isotype Control (antibody)

RRID:AB_10829607

This monoclonal targets Mouse (G3A1) mAb IgG1 Isotype Control

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Calreticulin, pAb (antibody)

RRID:AB_10618853

This polyclonal targets Calreticulin pAb

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CD 34, CD 34, Hematopoietic progenitor cell antigen, class II (antibody)

RRID:AB_2063006

This monoclonal targets Endothelial cell membranes obtained as vesicles from human placenta

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TGN46 Antibody (antibody)

RRID:AB_10011761

This unknown targets TGN46

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Calnexin, pAb (antibody)

RRID:AB_10616095

This polyclonal targets Calnexin pAb

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GRP 78 (C-20) (antibody)

RRID:AB_2119994

This polyclonal targets GRP 78 (C-20)

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BeWo (cell line)

RRID:CVCL_0044

Cell line BeWo is a Cancer cell line with a species of origin Homo sapiens (Human)

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GRP 78 (C-20) (antibody)

RRID:AB_2119994

This polyclonal targets GRP 78 (C-20)

View all literature mentions

CD 34, CD 34, Hematopoietic progenitor cell antigen, class II (antibody)

RRID:AB_2063006

This monoclonal targets Endothelial cell membranes obtained as vesicles from human placenta

View all literature mentions

Cytokeratin 7 (antibody)

RRID:AB_2134589

This monoclonal targets OTN 11, ovarian carcinoma cell line (1, 8).

View all literature mentions

Calreticulin, pAb (antibody)

RRID:AB_10618853

This polyclonal targets Calreticulin pAb

View all literature mentions

Mouse (G3A1) mAb IgG1 Isotype Control (antibody)

RRID:AB_10829607

This monoclonal targets Mouse (G3A1) mAb IgG1 Isotype Control

View all literature mentions

BeWo (cell line)

RRID:CVCL_0044

Cell line BeWo is a Cancer cell line with a species of origin Homo sapiens (Human)

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GM130 antibody [EP892Y] (antibody)

RRID:AB_880266

This monoclonal targets GM130 antibody [EP892Y]

View all literature mentions

Purified Mouse Anti-E-cadherin (antibody)

RRID:AB_397580

This monoclonal targets E-cadherin

View all literature mentions

Calnexin, pAb (antibody)

RRID:AB_10616095

This polyclonal targets Calnexin pAb

View all literature mentions

BeWo (cell line)

RRID:CVCL_0044

Cell line BeWo is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

TGN46 Antibody (antibody)

RRID:AB_10011761

This unknown targets TGN46

View all literature mentions

ERp57, pAb (antibody)

RRID:AB_10616507

This polyclonal targets ERp57 pAb

View all literature mentions

BeWo (cell line)

RRID:CVCL_0044

Cell line BeWo is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions