PUBLICATION
The different roles of V-ATPase a subunits in phagocytosis/endocytosis and autophagy
- Authors
- Chen, Q., Kou, H., Demy, D.L., Liu, W., Li, J., Wen, Z., Herbomel, P., Huang, Z., Zhang, W., Xu, J.
- ID
- ZDB-PUB-240615-2
- Date
- 2024
- Source
- Autophagy 20(10): 2297-2313 (Journal)
- Registered Authors
- Demy, Doris-Lou, Herbomel, Philippe, Huang, Zhibin, Liu, Wei, Xu, Jin, Zhang, Wenqing
- Keywords
- Autophagy, V-ATPase, microglia, phagosome maturation, zebrafish
- MeSH Terms
-
- Microglia/metabolism
- Mutation/genetics
- Autophagy*/physiology
- Endocytosis*/physiology
- Protein Subunits/metabolism
- Lysosomes*/metabolism
- Phagosomes*/metabolism
- Vacuolar Proton-Translocating ATPases*/metabolism
- Zebrafish*
- Phagocytosis*/physiology
- Animals
- Mice
- PubMed
- 38873931 Full text @ Autophagy
Citation
Chen, Q., Kou, H., Demy, D.L., Liu, W., Li, J., Wen, Z., Herbomel, P., Huang, Z., Zhang, W., Xu, J. (2024) The different roles of V-ATPase a subunits in phagocytosis/endocytosis and autophagy. Autophagy. 20(10):2297-2313.
Abstract
Microglia are specialized macrophages responsible for the clearance of dead neurons and pathogens by phagocytosis and degradation. The degradation requires phagosome maturation and acidification provided by the vesicular- or vacuolar-type H+-translocating adenosine triphosphatase (V-ATPase), which is composed of the cytoplasmic V1 domain and the membrane-embedded Vo domain. The V-ATPase a subunit, an integral part of the Vo domain, has four isoforms in mammals. The functions of different isoforms on phagosome maturation in different cells/species remain controversial. Here we show that mutations of both the V-ATPase Atp6v0a1 and Tcirg1b/Atp6v0a3 subunits lead to the accumulation of phagosomes in zebrafish microglia. However, their mechanisms are different. The V-ATPase Atp6v0a1 subunit is mainly distributed in early and late phagosomes. Defects of this subunit lead to a defective transition from early phagosomes to late phagosomes. In contrast, The V-ATPase Tcirg1b/Atp6v0a3 subunit is primarily located on lysosomes and regulates late phagosome-lysosomal fusion. Defective Tcirg1b/Atp6v0a3, but not Atp6v0a1 subunit leads to reduced acidification and impaired macroautophagy/autophagy in microglia. We further showed that ATP6V0A1/a1 and TCIRG1/a3 subunits in mouse macrophages preferentially located in endosomes and lysosomes, respectively. Blocking these subunits disrupted early-to-late endosome transition and endosome-to-lysosome fusion, respectively. Taken together, our results highlight the essential and conserved roles played by different V-ATPase subunits in multiple steps of phagocytosis and endocytosis across various species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping