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TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity
Centrosomes are composed of a centriolar core surrounded by pericentriolar material that nucleates microtubules. The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. We show that TRIM37 does not control centriole duplication, structure, or the ability...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127006/ https://www.ncbi.nlm.nih.gov/pubmed/33983387 http://dx.doi.org/10.1083/jcb.202010180 |
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author | Meitinger, Franz Kong, Dong Ohta, Midori Desai, Arshad Oegema, Karen Loncarek, Jadranka |
author_facet | Meitinger, Franz Kong, Dong Ohta, Midori Desai, Arshad Oegema, Karen Loncarek, Jadranka |
author_sort | Meitinger, Franz |
collection | PubMed |
description | Centrosomes are composed of a centriolar core surrounded by pericentriolar material that nucleates microtubules. The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. We show that TRIM37 does not control centriole duplication, structure, or the ability of centrioles to form cilia but instead prevents assembly of an ectopic centrobin-scaffolded structured condensate that forms by budding off of centrosomes. In ∼25% of TRIM37-deficient cells, the condensate organizes an ectopic spindle pole, recruiting other centrosomal proteins and acquiring microtubule nucleation capacity during mitotic entry. Ectopic spindle pole–associated transient multipolarity and multipolar segregation in TRIM37-deficient cells are suppressed by removing centrobin, which interacts with and is ubiquitinated by TRIM37. Thus, TRIM37 ensures accurate chromosome segregation by preventing the formation of centrobin-scaffolded condensates that organize ectopic spindle poles. Mutations in TRIM37 cause the disorder mulibrey nanism, and patient-derived cells harbor centrobin condensate-organized ectopic poles, leading us to propose that chromosome missegregation is a pathological mechanism in this disorder. |
format | Online Article Text |
id | pubmed-8127006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81270062022-01-05 TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity Meitinger, Franz Kong, Dong Ohta, Midori Desai, Arshad Oegema, Karen Loncarek, Jadranka J Cell Biol Article Centrosomes are composed of a centriolar core surrounded by pericentriolar material that nucleates microtubules. The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. We show that TRIM37 does not control centriole duplication, structure, or the ability of centrioles to form cilia but instead prevents assembly of an ectopic centrobin-scaffolded structured condensate that forms by budding off of centrosomes. In ∼25% of TRIM37-deficient cells, the condensate organizes an ectopic spindle pole, recruiting other centrosomal proteins and acquiring microtubule nucleation capacity during mitotic entry. Ectopic spindle pole–associated transient multipolarity and multipolar segregation in TRIM37-deficient cells are suppressed by removing centrobin, which interacts with and is ubiquitinated by TRIM37. Thus, TRIM37 ensures accurate chromosome segregation by preventing the formation of centrobin-scaffolded condensates that organize ectopic spindle poles. Mutations in TRIM37 cause the disorder mulibrey nanism, and patient-derived cells harbor centrobin condensate-organized ectopic poles, leading us to propose that chromosome missegregation is a pathological mechanism in this disorder. Rockefeller University Press 2021-05-13 /pmc/articles/PMC8127006/ /pubmed/33983387 http://dx.doi.org/10.1083/jcb.202010180 Text en © 2021 Meitinger et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Meitinger, Franz Kong, Dong Ohta, Midori Desai, Arshad Oegema, Karen Loncarek, Jadranka TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
title | TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
title_full | TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
title_fullStr | TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
title_full_unstemmed | TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
title_short | TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
title_sort | trim37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127006/ https://www.ncbi.nlm.nih.gov/pubmed/33983387 http://dx.doi.org/10.1083/jcb.202010180 |
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