Phagosome resolution regenerates lysosomes and maintains the degradative capacity in phagocytes
| Autor: | Roberto J. Botelho, Vanessa Jacobelli, Alex Somerville, Elliott Somerville, Roaya M. Dayam, Mauricio R. Terebiznik, Charlene E. Lancaster, Aaron Fountain, Javal Sheth |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Phagocytosis
Green Fluorescent Proteins Gene Expression Membrane Fusion Microtubules Clathrin Exocytosis Mice 03 medical and health sciences 0302 clinical medicine Membrane fission Genes Reporter Phagosomes Lysosome Phagosome maturation Escherichia coli medicine Animals Fragmentation (cell biology) 030304 developmental biology Phagosome 0303 health sciences biology Chemistry Vesicle Cell Biology Actins Cell biology Actin Cytoskeleton RAW 264.7 Cells medicine.anatomical_structure Proteolysis biology.protein Lysosomes 030217 neurology & neurosurgery |
| DOI: | 10.1101/2020.05.14.094722 |
| Popis: | During phagocytosis, phagocytes like macrophages engulf and sequester unwanted particles like bacteria into phagosomes. Phagosomes then fuse with lysosomes to mature into phagolysosomes, resulting in the degradation of the enclosed particle. Ultimately, phagosomes must be recycled to help recover membrane resources like lysosomes consumed during phagocytosis, a process referred to as phagosome resolution. Little is known about phagosome resolution, which may proceed through exocytosis or membrane fission. Here, we show that bacteria-containing phagolysosomes in macrophages undergo fragmentation through vesicle budding, tubulation, and constriction. Phagosome fragmentation required cargo degradation, the actin and microtubule cytoskeletons, and clathrin. We provide evidence that lysosome reformation occurs during phagosome resolution since the majority of phagosome-derived vesicles displayed lysosomal properties. Importantly, we showed that the clathrin-dependent phagosome resolution is important to maintain the degradative capacity of macrophages challenged with two waves of phagocytosis. Overall, our work suggests that phagosome resolution contributes to lysosome recovery and to maintain the degradative power of macrophages to handle multiple waves of phagocytosis. Summary Phagocytes engulf particles into phagolysosomes for degradation. However, the ultimate fate of phagolysosomes is undefined. Lancaster, Fountain et al. show that phagosomes undergo fragmentation to reform lysosomes in a clathrin-dependent manner. This process is necessary to maintain the degradative capacity of phagocytes during subsequent phagocytosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|