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Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow

Endomitosis is a special type of mitosis in which only cytokinesis—the final step of the cell division cycle—is defective, resulting in polyploid cells. Although endomitosis is biologically important, its regulatory aspects remain elusive. Psychosine, a lysogalactosylceramide, prevents proper cytoki...

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Autores principales: Watanabe, Hiroshi, Okahara, Kyohei, Naito-Matsui, Yuko, Abe, Mitsuhiro, Go, Shinji, Inokuchi, Jinichi, Okazaki, Toshiro, Kobayashi, Toshihide, Kozutsumi, Yasunori, Oka, Shogo, Takematsu, Hiromu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927278/
https://www.ncbi.nlm.nih.gov/pubmed/27170180
http://dx.doi.org/10.1091/mbc.E15-08-0555
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author Watanabe, Hiroshi
Okahara, Kyohei
Naito-Matsui, Yuko
Abe, Mitsuhiro
Go, Shinji
Inokuchi, Jinichi
Okazaki, Toshiro
Kobayashi, Toshihide
Kozutsumi, Yasunori
Oka, Shogo
Takematsu, Hiromu
author_facet Watanabe, Hiroshi
Okahara, Kyohei
Naito-Matsui, Yuko
Abe, Mitsuhiro
Go, Shinji
Inokuchi, Jinichi
Okazaki, Toshiro
Kobayashi, Toshihide
Kozutsumi, Yasunori
Oka, Shogo
Takematsu, Hiromu
author_sort Watanabe, Hiroshi
collection PubMed
description Endomitosis is a special type of mitosis in which only cytokinesis—the final step of the cell division cycle—is defective, resulting in polyploid cells. Although endomitosis is biologically important, its regulatory aspects remain elusive. Psychosine, a lysogalactosylceramide, prevents proper cytokinesis when supplemented to proliferating cells. Cytokinetic inhibition by psychosine does not inhibit genome duplication. Consequently cells undergo multiple rounds of endomitotic cell cycles, resulting in the formation of giant multiploid cells. Here we successfully quantified psychosine-triggered multiploid cell formation, showing that membrane sphingolipids ratios modulate psychosine-triggered polyploidy in Namalwa cells. Among enzymes that experimentally remodel cellular sphingolipids, overexpression of glucosylceramide synthase to biosynthesize glycosylsphingolipids (GSLs) and neutral sphingomyelinase 2 to hydrolyze sphingomyelin (SM) additively enhanced psychosine-triggered multiploidy; almost all of the cells became polyploid. In the presence of psychosine, Namalwa cells showed attenuated cell surface SM clustering and suppression of phosphatidylinositol 4,5-bisphosphate production at the cleavage furrow, both important processes for cytokinesis. Depending on the sphingolipid balance between GSLs and SM, Namalwa cells could be effectively converted to viable multiploid cells with psychosine.
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spelling pubmed-49272782016-09-16 Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow Watanabe, Hiroshi Okahara, Kyohei Naito-Matsui, Yuko Abe, Mitsuhiro Go, Shinji Inokuchi, Jinichi Okazaki, Toshiro Kobayashi, Toshihide Kozutsumi, Yasunori Oka, Shogo Takematsu, Hiromu Mol Biol Cell Articles Endomitosis is a special type of mitosis in which only cytokinesis—the final step of the cell division cycle—is defective, resulting in polyploid cells. Although endomitosis is biologically important, its regulatory aspects remain elusive. Psychosine, a lysogalactosylceramide, prevents proper cytokinesis when supplemented to proliferating cells. Cytokinetic inhibition by psychosine does not inhibit genome duplication. Consequently cells undergo multiple rounds of endomitotic cell cycles, resulting in the formation of giant multiploid cells. Here we successfully quantified psychosine-triggered multiploid cell formation, showing that membrane sphingolipids ratios modulate psychosine-triggered polyploidy in Namalwa cells. Among enzymes that experimentally remodel cellular sphingolipids, overexpression of glucosylceramide synthase to biosynthesize glycosylsphingolipids (GSLs) and neutral sphingomyelinase 2 to hydrolyze sphingomyelin (SM) additively enhanced psychosine-triggered multiploidy; almost all of the cells became polyploid. In the presence of psychosine, Namalwa cells showed attenuated cell surface SM clustering and suppression of phosphatidylinositol 4,5-bisphosphate production at the cleavage furrow, both important processes for cytokinesis. Depending on the sphingolipid balance between GSLs and SM, Namalwa cells could be effectively converted to viable multiploid cells with psychosine. The American Society for Cell Biology 2016-07-01 /pmc/articles/PMC4927278/ /pubmed/27170180 http://dx.doi.org/10.1091/mbc.E15-08-0555 Text en © 2016 Watanabe et al. 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). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Watanabe, Hiroshi
Okahara, Kyohei
Naito-Matsui, Yuko
Abe, Mitsuhiro
Go, Shinji
Inokuchi, Jinichi
Okazaki, Toshiro
Kobayashi, Toshihide
Kozutsumi, Yasunori
Oka, Shogo
Takematsu, Hiromu
Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
title Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
title_full Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
title_fullStr Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
title_full_unstemmed Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
title_short Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
title_sort psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927278/
https://www.ncbi.nlm.nih.gov/pubmed/27170180
http://dx.doi.org/10.1091/mbc.E15-08-0555
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