pH of endophagosomes controls association of their membranes with Vps34 and PtdIns(3)P levels
| Autor: | Akriti Prashar, Victoria E. B. Hipolito, Roberto J. Botelho, Mauricio R. Terebiznik, Suriakarthiga Ganesan, Amriya Naufer, Vanina Zaremberg |
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| Rok vydání: | 2023 |
| Předmět: |
0301 basic medicine
Endosome Phagocytosis Endosomes Biology Article Cell Line Legionella pneumophila Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences PIKFYVE Phagosomes Organelle Animals Research Articles rab5 GTP-Binding Proteins Phagosome Macrophages Cell Membrane rab7 GTP-Binding Proteins Cell Biology Hydrogen-Ion Concentration Class III Phosphatidylinositol 3-Kinases Cell biology RAW 264.7 Cells 030104 developmental biology Membrane rab GTP-Binding Proteins Cell culture Signal transduction Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| DOI: | 10.32920/21982907 |
| Popis: | Specific changes in phospholipid content are a hallmark of the membranes of maturing endosomes and phagosomes, but is it unclear how this is controlled. Naufer et al. now show that acidification of the lumen of endosomes and phagosomes triggers dissociation of the Vps34 lipid kinase from these organelles, which terminates PtdIns(3)P synthesis and signaling. Phagocytosis of filamentous bacteria occurs through tubular phagocytic cups (tPCs) and takes many minutes to engulf these filaments into phagosomes. Contravening the canonical phagocytic pathway, tPCs mature by fusing with endosomes. Using this model, we observed the sequential recruitment of early and late endolysosomal markers to the elongating tPCs. Surprisingly, the regulatory early endosomal lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) persists on tPCs as long as their luminal pH remains neutral. Interestingly, by manipulating cellular pH, we determined that PtdIns(3)P behaves similarly in canonical phagosomes as well as endosomes. We found that this is the product of a pH-based mechanism that induces the dissociation of the Vps34 class III phosphatidylinositol-3-kinase from these organelles as they acidify. The detachment of Vps34 stops the production of PtdIns(3)P, allowing for the turnover of this lipid by PIKfyve. Given that PtdIns(3)P-dependent signaling is important for multiple cellular pathways, this mechanism for pH-dependent regulation of Vps34 could be at the center of many PtdIns(3)P-dependent cellular processes. |
| Databáze: | OpenAIRE |
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