TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin
TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we characterize these centriolar protein assemblies...
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2021-01-01
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doaj-43c73efe37f44b62a2ac44ad88b4b1c62021-05-05T22:43:02ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.62640TRIM37 prevents formation of centriolar protein assemblies by regulating CentrobinFernando R Balestra0https://orcid.org/0000-0003-2741-6068Andrés Domínguez-Calvo1https://orcid.org/0000-0002-3689-227XBenita Wolf2https://orcid.org/0000-0001-5673-4239Coralie Busso3Alizée Buff4Tessa Averink5Marita Lipsanen-Nyman6Pablo Huertas7https://orcid.org/0000-0002-1756-4449Rosa M Ríos8Pierre Gönczy9https://orcid.org/0000-0002-6305-6883Departamento de Genética, Universidad de Sevilla, Sevilla, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, SpainDepartamento de Genética, Universidad de Sevilla, Sevilla, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, SpainSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandPediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartamento de Genética, Universidad de Sevilla, Sevilla, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, SpainCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, SpainSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandTRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we characterize these centriolar protein assemblies (Cenpas) to uncover the mechanism of action of TRIM37. We find that an atypical de novo assembly pathway can generate Cenpas that act as microtubule-organizing centers (MTOCs), including in Mulibrey patient cells. Correlative light electron microscopy reveals that Cenpas are centriole-related or electron-dense structures with stripes. TRIM37 regulates the stability and solubility of Centrobin, which accumulates in elongated entities resembling the striped electron dense structures upon TRIM37 depletion. Furthermore, Cenpas formation upon TRIM37 depletion requires PLK4, as well as two parallel pathways relying respectively on Centrobin and PLK1. Overall, our work uncovers how TRIM37 prevents Cenpas formation, which would otherwise threaten genome integrity.https://elifesciences.org/articles/62640TRIM37 E3 ligaseMulibrey nanismCentriolemicrotubule organizing centercentrobinCLEM |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fernando R Balestra Andrés Domínguez-Calvo Benita Wolf Coralie Busso Alizée Buff Tessa Averink Marita Lipsanen-Nyman Pablo Huertas Rosa M Ríos Pierre Gönczy |
spellingShingle |
Fernando R Balestra Andrés Domínguez-Calvo Benita Wolf Coralie Busso Alizée Buff Tessa Averink Marita Lipsanen-Nyman Pablo Huertas Rosa M Ríos Pierre Gönczy TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin eLife TRIM37 E3 ligase Mulibrey nanism Centriole microtubule organizing center centrobin CLEM |
author_facet |
Fernando R Balestra Andrés Domínguez-Calvo Benita Wolf Coralie Busso Alizée Buff Tessa Averink Marita Lipsanen-Nyman Pablo Huertas Rosa M Ríos Pierre Gönczy |
author_sort |
Fernando R Balestra |
title |
TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin |
title_short |
TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin |
title_full |
TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin |
title_fullStr |
TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin |
title_full_unstemmed |
TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin |
title_sort |
trim37 prevents formation of centriolar protein assemblies by regulating centrobin |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-01-01 |
description |
TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we characterize these centriolar protein assemblies (Cenpas) to uncover the mechanism of action of TRIM37. We find that an atypical de novo assembly pathway can generate Cenpas that act as microtubule-organizing centers (MTOCs), including in Mulibrey patient cells. Correlative light electron microscopy reveals that Cenpas are centriole-related or electron-dense structures with stripes. TRIM37 regulates the stability and solubility of Centrobin, which accumulates in elongated entities resembling the striped electron dense structures upon TRIM37 depletion. Furthermore, Cenpas formation upon TRIM37 depletion requires PLK4, as well as two parallel pathways relying respectively on Centrobin and PLK1. Overall, our work uncovers how TRIM37 prevents Cenpas formation, which would otherwise threaten genome integrity. |
topic |
TRIM37 E3 ligase Mulibrey nanism Centriole microtubule organizing center centrobin CLEM |
url |
https://elifesciences.org/articles/62640 |
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