Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation.

Détails

Ressource 1Télécharger: 41467_2019_Article_14009.pdf (4404.30 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_61F53FCBFD55
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation.
Périodique
Nature communications
Auteur⸱e⸱s
Hämälistö S., Stahl J.L., Favaro E., Yang Q., Liu B., Christoffersen L., Loos B., Guasch Boldú C., Joyce J.A., Reinheckel T., Barisic M., Jäättelä M.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
13/01/2020
Peer-reviewed
Oui
Volume
11
Numéro
1
Pages
229
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Lysosomes are membrane-surrounded cytoplasmic organelles filled with a powerful cocktail of hydrolases. Besides degrading cellular constituents inside the lysosomal lumen, lysosomal hydrolases promote tissue remodeling when delivered to the extracellular space and cell death when released to the cytosol. Here, we show that spatially and temporally controlled lysosomal leakage contributes to the accurate chromosome segregation in normal mammalian cell division. One or more chromatin-proximal lysosomes leak in the majority of prometaphases, after which active cathepsin B (CTSB) localizes to the metaphase chromatin and cleaves a small subset of histone H3. Stabilization of lysosomal membranes or inhibition of CTSB activity during mitotic entry results in a significant increase in telomere-related chromosome segregation defects, whereas cells and tissues lacking CTSB and cells expressing CTSB-resistant histone H3 accumulate micronuclei and other nuclear defects. These data suggest that lysosomal leakage and chromatin-associated CTSB contribute to proper chromosome segregation and maintenance of genomic integrity.
Mots-clé
Animals, Cathepsin B/antagonists & inhibitors, Cathepsin B/genetics, Cathepsin B/metabolism, Cell Line, Cell Nucleus/genetics, Cell Nucleus/pathology, Chromatin/metabolism, Chromosome Segregation/genetics, Female, Gene Silencing, Histones/metabolism, Humans, Intracellular Membranes/metabolism, Lysosomes/enzymology, Lysosomes/metabolism, Metaphase, Mice, Mitosis/genetics, Permeability, Telomere/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/01/2020 16:14
Dernière modification de la notice
21/11/2022 8:26
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