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Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells
Vimentin, a type III intermediate filament (IF) protein, is phosphorylated predominantly in mitosis. The expression of a phosphorylation-compromised vimentin mutant in T24 cultured cells leads to cytokinetic failure, resulting in binucleation (multinucleation). The physiological significance of inte...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861614/ https://www.ncbi.nlm.nih.gov/pubmed/24142690 http://dx.doi.org/10.1074/jbc.M113.514737 |
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author | Matsuyama, Makoto Tanaka, Hiroki Inoko, Akihito Goto, Hidemasa Yonemura, Shigenobu Kobori, Kyoko Hayashi, Yuko Kondo, Eisaku Itohara, Shigeyoshi Izawa, Ichiro Inagaki, Masaki |
author_facet | Matsuyama, Makoto Tanaka, Hiroki Inoko, Akihito Goto, Hidemasa Yonemura, Shigenobu Kobori, Kyoko Hayashi, Yuko Kondo, Eisaku Itohara, Shigeyoshi Izawa, Ichiro Inagaki, Masaki |
author_sort | Matsuyama, Makoto |
collection | PubMed |
description | Vimentin, a type III intermediate filament (IF) protein, is phosphorylated predominantly in mitosis. The expression of a phosphorylation-compromised vimentin mutant in T24 cultured cells leads to cytokinetic failure, resulting in binucleation (multinucleation). The physiological significance of intermediate filament phosphorylation during mitosis for organogenesis and tissue homeostasis was uncertain. Here, we generated knock-in mice expressing vimentin that have had the serine sites phosphorylated during mitosis substituted by alanine residues. Homozygotic mice (VIM(SA/SA)) presented with microophthalmia and cataracts in the lens, whereas heterozygotic mice (VIM(WT/SA)) were indistinguishable from WT (VIM(WT/WT)) mice. In VIM(SA/SA) mice, lens epithelial cell number was not only reduced but the cells also exhibited chromosomal instability, including binucleation and aneuploidy. Electron microscopy revealed fiber membranes that were disorganized in the lenses of VIM(SA/SA), reminiscent of similar characteristic changes seen in age-related cataracts. Because the mRNA level of the senescence (aging)-related gene was significantly elevated in samples from VIM(SA/SA), the lens phenotype suggests a possible causal relationship between chromosomal instability and premature aging. |
format | Online Article Text |
id | pubmed-3861614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-38616142013-12-18 Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells Matsuyama, Makoto Tanaka, Hiroki Inoko, Akihito Goto, Hidemasa Yonemura, Shigenobu Kobori, Kyoko Hayashi, Yuko Kondo, Eisaku Itohara, Shigeyoshi Izawa, Ichiro Inagaki, Masaki J Biol Chem Cell Biology Vimentin, a type III intermediate filament (IF) protein, is phosphorylated predominantly in mitosis. The expression of a phosphorylation-compromised vimentin mutant in T24 cultured cells leads to cytokinetic failure, resulting in binucleation (multinucleation). The physiological significance of intermediate filament phosphorylation during mitosis for organogenesis and tissue homeostasis was uncertain. Here, we generated knock-in mice expressing vimentin that have had the serine sites phosphorylated during mitosis substituted by alanine residues. Homozygotic mice (VIM(SA/SA)) presented with microophthalmia and cataracts in the lens, whereas heterozygotic mice (VIM(WT/SA)) were indistinguishable from WT (VIM(WT/WT)) mice. In VIM(SA/SA) mice, lens epithelial cell number was not only reduced but the cells also exhibited chromosomal instability, including binucleation and aneuploidy. Electron microscopy revealed fiber membranes that were disorganized in the lenses of VIM(SA/SA), reminiscent of similar characteristic changes seen in age-related cataracts. Because the mRNA level of the senescence (aging)-related gene was significantly elevated in samples from VIM(SA/SA), the lens phenotype suggests a possible causal relationship between chromosomal instability and premature aging. American Society for Biochemistry and Molecular Biology 2013-12-13 2013-10-18 /pmc/articles/PMC3861614/ /pubmed/24142690 http://dx.doi.org/10.1074/jbc.M113.514737 Text en © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles |
spellingShingle | Cell Biology Matsuyama, Makoto Tanaka, Hiroki Inoko, Akihito Goto, Hidemasa Yonemura, Shigenobu Kobori, Kyoko Hayashi, Yuko Kondo, Eisaku Itohara, Shigeyoshi Izawa, Ichiro Inagaki, Masaki Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells |
title | Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells |
title_full | Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells |
title_fullStr | Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells |
title_full_unstemmed | Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells |
title_short | Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells |
title_sort | defect of mitotic vimentin phosphorylation causes microophthalmia and cataract via aneuploidy and senescence in lens epithelial cells |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861614/ https://www.ncbi.nlm.nih.gov/pubmed/24142690 http://dx.doi.org/10.1074/jbc.M113.514737 |
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