scholarly journals ZO-1 is involved in trophoblastic cell differentiation in human placenta

2010 ◽  
Vol 298 (6) ◽  
pp. C1517-C1526 ◽  
Author(s):  
Guillaume Pidoux ◽  
Pascale Gerbaud ◽  
Sédami Gnidehou ◽  
Michael Grynberg ◽  
Graziello Geneau ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Cell Fusion ◽  
Physical Interaction ◽  
Placental Development ◽  
Trophoblastic Cell ◽  
Cx43 Expression ◽  
Human Trophoblast ◽  
Trophoblastic Cells ◽  
Zona Occludens ◽  
Cell Cell

Trophoblastic cell-cell fusion is an essential event required during human placental development. Several membrane proteins have been described to be directly involved in this process, including connexin 43 (Cx43), syncytin 1 (Herv-W env), and syncytin 2 (Herv-FRD env glycoprotein). Recently, zona occludens (ZO) proteins (peripheral membrane proteins associated with tight junctions, adherens junctions, and gap junctions) were shown to be involved in mouse placental development. Moreover, zona occludens 1 (ZO-1) was localized mainly at the intercellular boundaries between human trophoblastic cells. Therefore the role of ZO-1 in the dynamic process of human trophoblastic cell-cell fusion was investigated using primary trophoblastic cells in culture. In vitro as in situ, ZO-1 was localized mainly at the intercellular boundaries between trophoblastic cells where its expression substantially decreased during differentiation and during fusion. At the same time, Cx43 was localized at the interface of trophoblastic cells and its expression increased during differentiation. To determine a functional role for ZO-1 during trophoblast differentiation, small interfering RNA (siRNA) was used to knock down ZO-1 expression. Cytotrophoblasts treated with ZO-1 siRNA fused poorly, but interestingly, decreased Cx43 expression without altering the functionality of trophoblastic cell-cell communication as measured by relative permeability time constant determined using gap-FRAP experiments. Because kinetics of Cx43 and ZO-1 proteins show a mirror image, a potential association of these two proteins was investigated. By using coimmunoprecipitation experiments, a physical interaction between ZO-1 and Cx43 was demonstrated. These results demonstrate that a decrease in ZO-1 expression reduces human trophoblast cell-cell fusion and differentiation.

Human Trophoblast in Trisomy 21: A Model for Cell–Cell Fusion Dynamic Investigation

2011 ◽  
pp. 103-112 ◽  
Author(s):  
André Malassiné ◽  
Guillaume Pidoux ◽  
Pascale Gerbaud ◽  
Jean Louis Frendo ◽  
Danièle Evain-Brion
Keyword(s):  
Cell Fusion ◽  
Trisomy 21 ◽  
Human Trophoblast ◽  
Dynamic Investigation ◽  
Cell Cell

scholarly journals TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development

2019 ◽  
Author(s):  
Yang Zhang ◽  
Trieu Le ◽  
Ryan Grabau ◽  
Zahra Mohseni ◽  
Hoejeong Kim ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Fusion ◽  
Placental Development ◽  
Cellular Mechanisms ◽  
Developmental Defects ◽  
Phospholipid Scramblase ◽  
A Cell ◽  
Fusion Signal ◽  
Multicellular Organisms ◽  
Cell Cell

AbstractCell-cell fusion or syncytialization is fundamental to the reproduction, development and homeostasis of multicellular organisms. In addition to various cell-type specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell-fusion events. Nevertheless, molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here we report that TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), plays an indispensable role in placental trophoblast fusion by translocating PS to the cell surface independent of apoptosis. Consistent with its essential role in trophoblast fusion, the placentas from TMEM16F-deficient mice exhibit deficiency in syncytialization, placental developmental defects and perinatal lethality. Our findings thus identify a cell-cell fusion mechanism by which TMEM16F CaPLSase-dependent externalization of PS serves as a critical cell fusion signal to facilitate trophoblast syncytialization and placental development.

scholarly journals A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ka Man Carmen Chan ◽  
Sungmin Son ◽  
Eva M Schmid ◽  
Daniel A Fletcher
Keyword(s):  
Membrane Proteins ◽  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Conformational Changes ◽  
Close Contact ◽  
Adaptor Protein ◽  
Cytoplasmic Domain ◽  
Actin Assembly ◽  
Actin Network ◽  
Cell Cell

Cell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that phosphorylation of the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network. Using p14 mutants, we demonstrate that fusion is abrogated when binding of an adaptor protein is prevented and that direct coupling of the fusogenic ectodomain to branched actin assembly is sufficient to drive cell-cell fusion. This work reveals how the actin cytoskeleton can be harnessed to overcome energetic barriers to cell-cell fusion.

scholarly journals TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development

2020 ◽  
Vol 6 (19) ◽  
pp. eaba0310 ◽  
Author(s):  
Yang Zhang ◽  
Trieu Le ◽  
Ryan Grabau ◽  
Zahra Mohseni ◽  
Hoejeong Kim ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Fusion ◽  
Cell Types ◽  
Placental Development ◽  
Cellular Mechanisms ◽  
Phospholipid Scramblase ◽  
Perinatal Lethality ◽  
Cell Type Specific ◽  
Multicellular Organisms ◽  
Cell Cell

Cell-cell fusion or syncytialization is fundamental to the reproduction, development, and homeostasis of multicellular organisms. In addition to various cell type–specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell fusion events. Nevertheless, the molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here, we report that TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), plays an essential role in placental trophoblast fusion by translocating PS to cell surface independent of apoptosis. The placentas from the TMEM16F knockout mice exhibit deficiency in trophoblast syncytialization and placental development, which lead to perinatal lethality. We thus identified a new biological function of TMEM16F CaPLSase in trophoblast fusion and placental development. Our findings provide insight into understanding cell-cell fusion mechanism of other cell types and on mitigating pregnancy complications such as miscarriage, intrauterine growth restriction, and preeclampsia.

scholarly journals A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion

2019 ◽  
Author(s):  
Ka Man Carmen Chan ◽  
Sungmin Son ◽  
Eva M. Schmid ◽  
Daniel A. Fletcher
Keyword(s):  
Membrane Proteins ◽  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Conformational Changes ◽  
Close Contact ◽  
Cytoplasmic Domain ◽  
Force Generation ◽  
Actin Assembly ◽  
Actin Network ◽  
Cell Cell

AbstractCell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network, directly coupling local force generation with a short membrane-disruptive ectodomain. This work reveals that overcoming energetic barriers to cell-cell fusion does not require conformational changes of tall fusogens but can instead be driven by harnessing the host cytoskeleton.Impact StatementA viral fusogen drives cell-cell fusion by hijacking the actin machinery to directly couple actin assembly with a short fusogenic ectodomain.

scholarly journals Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6130 ◽  
Author(s):  
Yoshiyuki Yamada ◽  
Xiao Bo Liu ◽  
Shou Guo Fang ◽  
Felicia P. L. Tay ◽  
Ding Xiang Liu
Keyword(s):  
Amino Acid ◽  
Cell Fusion ◽  
Cultured Cells ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
Fusion Activity ◽  
Cell Cell

scholarly journals Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yueyi Yang ◽  
Wenjing Liu ◽  
JieYa Wei ◽  
Yujia Cui ◽  
Demao Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gap Junction ◽  
Cell Line ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cx43 Expression ◽  
Mc3t3 Cell ◽  
Primary Osteoblasts ◽  
Tgf Β1 ◽  
Cell Cell

AbstractGap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.

scholarly journals Elizabeth Chen: Fusing cells press closer

2014 ◽  
Vol 206 (5) ◽  
pp. 576-577
Author(s):  
Caitlin Sedwick
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Chen studies cell–cell fusion in Drosophila myoblasts.

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