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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...

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Autores principales: Meitinger, Franz, Kong, Dong, Ohta, Midori, Desai, Arshad, Oegema, Karen, Loncarek, Jadranka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
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.
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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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