TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin
- CABIMER-University of Seville, Spain
- Swiss Federal Institute of Technology, Switzerland
- University of Helsinki, Finland
Abstract
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, including in Mulibrey patients.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Krebsforschung Schweiz (KFS-3388-02-2014)
- Pierre Gönczy
Marie Curie Actions (PIEF-GA-2013-629414)
- Fernando R Balestra
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Fibroblast cultures were established from skin biopsy samples with approval by the Institutional Review Board of the Helsinki University Central Hospital (183/13/03/03/2009). The patients signed an informed consent for the use of fibroblast cultures.
Copyright
© 2021, Balestra et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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