| Title: |
Transactive response DNA-binding protein 43 is enriched at the centrosome in human cells |
| Authors: |
Bodin, Alexia; Greibill, Logan; Gouju, Julien; Letournel, Franck; Pozzi, Silvia; Julien, Jean-Pierre; Renaud, Laurence; Bohl, Delphine; Millecamps, Stéphanie; Verny, Christophe; Cassereau, Julien; Lenaers, Guy; Chevrollier, Arnaud; Tassin, Anne-Marie; Codron, Philippe |
| Contributors: |
French National Scientific Research Council; French National Institute for Health and Medical Research; European Regional Development Fund; French Research Association on Amyotrophic Lateral Sclerosis; University Hospital of Angers; University of Angers |
| Source: |
Brain ; volume 146, issue 9, page 3624-3633 ; ISSN 0006-8950 1460-2156 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
The centrosome, as the main microtubule organizing centre, plays key roles in cell polarity, genome stability and ciliogenesis. The recent identification of ribosomes, RNA-binding proteins and transcripts at the centrosome suggests local protein synthesis. In this context, we hypothesized that TDP-43, a highly conserved RNA binding protein involved in the pathophysiology of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, could be enriched at this organelle. Using dedicated high magnification sub-diffraction microscopy on human cells, we discovered a novel localization of TDP-43 at the centrosome during all phases of the cell cycle. These results were confirmed on purified centrosomes by western blot and immunofluorescence microscopy. In addition, the co-localization of TDP-43 and pericentrin suggested a pericentriolar enrichment of the protein, leading us to hypothesize that TDP-43 might interact with local mRNAs and proteins. Supporting this hypothesis, we found four conserved centrosomal mRNAs and 16 centrosomal proteins identified as direct TDP-43 interactors. More strikingly, all the 16 proteins are implicated in the pathophysiology of TDP-43 proteinopathies, suggesting that TDP-43 dysfunction in this organelle contributes to neurodegeneration. This first description of TDP-43 centrosomal enrichment paves the way for a more comprehensive understanding of TDP-43 physiology and pathology. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/brain/awad228 |
| DOI: |
10.1093/brain/awad228/51009715/awad228.pdf |
| Availability: |
https://doi.org/10.1093/brain/awad228; https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awad228/51009715/awad228.pdf; https://academic.oup.com/brain/article-pdf/146/9/3624/51330802/awad228.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.6DD5962A |
| Database: |
BASE |