Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
Apr 2024
Apr 2024
Historique:
received:
08
12
2021
accepted:
20
02
2024
pubmed:
23
3
2024
medline:
23
3
2024
entrez:
23
3
2024
Statut:
ppublish
Résumé
Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis revealed a segregation of age-related protein dynamics with biological functions, including a downregulation of vesicle-mediated transport. We found a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis and lysosomal degradation. In gene deletion and overexpression experiments, Arf6 affected endocytosis pathways in endothelial cells. Our approach uncovered changes not picked up by transcriptomic studies, such as accumulation of vesicle cargo and receptor ligands, including Apoe. Proteomic analysis of BECs from Apoe-deficient mice revealed a signature of accelerated aging. Our findings provide a resource for analysing BEC function during aging.
Identifiants
pubmed: 38519806
doi: 10.1038/s43587-024-00598-z
pii: 10.1038/s43587-024-00598-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-612Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : DI 722/13-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : DI 722/16-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : BE 6169/1-1
Organisme : Fondation Leducq
ID : N022CVD01
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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