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Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion

Cell–cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3...

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Autores principales: Shibukawa, Yukinao, Yamazaki, Natsuko, Kumasawa, Keiichi, Daimon, Etsuko, Tajiri, Michiko, Okada, Yuka, Ikawa, Masahito, Wada, Yoshinao
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982094/
https://www.ncbi.nlm.nih.gov/pubmed/20861310
http://dx.doi.org/10.1091/mbc.E10-03-0261
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author Shibukawa, Yukinao
Yamazaki, Natsuko
Kumasawa, Keiichi
Daimon, Etsuko
Tajiri, Michiko
Okada, Yuka
Ikawa, Masahito
Wada, Yoshinao
author_facet Shibukawa, Yukinao
Yamazaki, Natsuko
Kumasawa, Keiichi
Daimon, Etsuko
Tajiri, Michiko
Okada, Yuka
Ikawa, Masahito
Wada, Yoshinao
author_sort Shibukawa, Yukinao
collection PubMed
description Cell–cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted BeWo cell fusion. CNN3 at the cytoplasmic face of cytoskeleton was dislocated from F-actin with forskolin treatment and diffused into the cytoplasm in a phosphorylation-dependent manner. Phosphorylation sites were located at Ser293/296 in the C-terminal region, and deletion of this region or site-specific disruption of Ser293/296 suppressed syncytium formation. These CNN3 mutants were colocalized with F-actin and remained there after forskolin treatment, suggesting that dissociation of CNN3 from F-actin is modulated by the phosphorylation status of the C-terminal region unique to CNN3 in the CNN family proteins. The mutant missing these phosphorylation sites displayed a dominant negative effect on cell fusion, while replacement of Ser293/296 with aspartic acid enhanced syncytium formation. These results indicated that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent.
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spelling pubmed-29820942011-01-30 Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion Shibukawa, Yukinao Yamazaki, Natsuko Kumasawa, Keiichi Daimon, Etsuko Tajiri, Michiko Okada, Yuka Ikawa, Masahito Wada, Yoshinao Mol Biol Cell Articles Cell–cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted BeWo cell fusion. CNN3 at the cytoplasmic face of cytoskeleton was dislocated from F-actin with forskolin treatment and diffused into the cytoplasm in a phosphorylation-dependent manner. Phosphorylation sites were located at Ser293/296 in the C-terminal region, and deletion of this region or site-specific disruption of Ser293/296 suppressed syncytium formation. These CNN3 mutants were colocalized with F-actin and remained there after forskolin treatment, suggesting that dissociation of CNN3 from F-actin is modulated by the phosphorylation status of the C-terminal region unique to CNN3 in the CNN family proteins. The mutant missing these phosphorylation sites displayed a dominant negative effect on cell fusion, while replacement of Ser293/296 with aspartic acid enhanced syncytium formation. These results indicated that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent. The American Society for Cell Biology 2010-11-15 /pmc/articles/PMC2982094/ /pubmed/20861310 http://dx.doi.org/10.1091/mbc.E10-03-0261 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Shibukawa, Yukinao
Yamazaki, Natsuko
Kumasawa, Keiichi
Daimon, Etsuko
Tajiri, Michiko
Okada, Yuka
Ikawa, Masahito
Wada, Yoshinao
Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion
title Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion
title_full Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion
title_fullStr Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion
title_full_unstemmed Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion
title_short Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion
title_sort calponin 3 regulates actin cytoskeleton rearrangement in trophoblastic cell fusion
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982094/
https://www.ncbi.nlm.nih.gov/pubmed/20861310
http://dx.doi.org/10.1091/mbc.E10-03-0261
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