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J Cell Biol. 2018 Jan 2;217(1):329-346. doi: 10.1083/jcb.201702179. Epub 2017 Oct 31.

pH of endophagosomes controls association of their membranes with Vps34 and PtdIns(3)P levels.

Author information

1
Department of Biological Sciences, University of Toronto Scarborough, Toronto, Canada.
2
Department of Cell and System Biology, University of Toronto Scarborough, Toronto, Canada.
3
Molecular Science Graduate Program, Ryerson University, Toronto, Canada.
4
Department of Chemistry and Biology, Ryerson University, Toronto, Canada.
5
Department of Biological Sciences, University of Calgary, Calgary, Canada.
6
Molecular Science Graduate Program, Ryerson University, Toronto, Canada rbotelho@ryerson.ca.
7
Department of Biological Sciences, University of Toronto Scarborough, Toronto, Canada terebiznik@utsc.utoronto.ca.

Abstract

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.

PMID:
29089378
PMCID:
PMC5748975
DOI:
10.1083/jcb.201702179
[Indexed for MEDLINE]
Free PMC Article

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