Single-phagosome imaging reveals that homotypic fusion impairs phagosome degradative function.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
10
08
2021
revised:
01
12
2021
accepted:
22
12
2021
pubmed:
31
12
2021
medline:
15
4
2022
entrez:
30
12
2021
Statut:
ppublish
Résumé
Immune cells degrade internalized pathogens in vesicle compartments called phagosomes. Many intracellular bacteria induce homotypic phagosome fusion to survive in host cells, but the fusion interaction between phagosomes and its consequence for phagosome function have scarcely been studied. Here, we characterize homotypic fusion between phagosomes in macrophages and identify how such interactions impact the degradative capacity of phagosomes. By developing a series of particle sensors for measuring biochemical changes of single phagosomes, we show that phagosomes undergo stable fusion, transient "kiss-and-run" fusion, or both in succession. Super-resolution three-dimensional fluorescence microscopy revealed that stably fused phagosomes are connected by membrane "necks" with submicron-sized fusion pores. Furthermore, we demonstrate that, after stable fusion, phagosomes have leaky membranes and thereby impaired degradative functions. Our findings, based on phagosomes that contain synthetic particles, illustrate that homotypic fusion is not exclusive to phagosomes that encapsulate pathogens, as previously believed. The physical process of homotypic fusion is alone sufficient to perturb the degradative functions of phagosomes.
Identifiants
pubmed: 34968424
pii: S0006-3495(21)03956-4
doi: 10.1016/j.bpj.2021.12.032
pmc: PMC8822610
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-469Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM124918
Pays : United States
Informations de copyright
Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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