Language

English

Publication Date

5-16-2025

Journal

iScience

DOI

10.1016/j.isci.2025.112371

PMID

40330883

PMCID

PMC12052997

PubMedCentral® Posted Date

4-8-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Phosphatidylinositol-3-phosphate (PI(3)P) is important for multiple functions of retinal pigmented epithelial (RPE) cells, but its functions in RPE have not been studied. In RPE from mouse eyes and in cultured human RPE cells, PI(3)P-enriched membranes include endosomes, the trans-Golgi network, phagosomes, and autophagophores. Mouse RPE cells lacking activity of the PI-3 kinase, Vps34, lack detectable PI(3)P and die prematurely. Phagosomes containing rod discs accumulate, as do membrane aggregates positive for autophagosome markers. These autophagy-related membranes recruit LC3/Atg8 without Vps34, but phagosomes do not. Vps34 loss leads to accumulation of lysosomes which do not fuse with phagosomes or membranes with autophagy markers. Thus, Vps34-derived PI(3)P is not needed for initiation of phagocytosis or endocytosis, nor for formation of membranes containing autophagy markers. In contrast, Vps34 and PI(3)P are essential for intermediate and later stages, including membrane fusion with lysosomes.

Keywords

Enzymology, Lipid, Membranes, Functional aspects of cell biology, Model organism

Published Open-Access

yes

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