Phagosome maturation during endosome interaction revealed by partial rhodopsin processing in retinal pigment epithelium
Open accessAbstract
Defects in phagocytosis and degradation of photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE) are associated with aging and retinal disease. The daily burst of rod outer segment (ROS) phagocytosis by the RPE provides a unique opportunity to analyse phagosome processing in vivo. In mouse retinae, phagosomes containing stacked rhodopsin-rich discs were identified by immuno-electron microscopy. Early apical phagosomes stained with antibodies against both cytoplasmic and intradiscal domains of rhodopsin. During phagosome maturation, a remarkably synchronised loss of the cytoplasmic epitope coincided with movement to the cell body and preceded phagosome-lysosome fusion and disc degradation. Loss of the intradiscal rhodopsin epitope and disc digestion occurred upon fusion with cathepsin-D-positive lysosomes. The same sequential stages of phagosome maturation were identified in cultured RPE and macrophages challenged with isolated POS. Loss of the cytoplasmic rhodopsin epitope was insensitive to pH but sensitive to protease inhibition and coincided with the interaction of phagosomes with endosomes. Thus, during pre-lysosomal maturation of ROS-containing phagosomes, limited rhodopsin processing occurs upon interaction with endosomes. This potentially provides a sensitive readout of phagosome-endosome interactions that is applicable to multiple phagocytes.
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POS phagosomes labeled by mAb 1D4 are present in the apical RPE.
“POS phagosomes labeled by this mAb are present in the apical RPE (Esteve-Rudd et al., 2014; Wavre-Shapton et al., 2014).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Wavre-Shapton et al., 2014
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- Authors
- Wavre-Shapton, S. T., Meschede, I. P., Seabra, M. C., & Futter, C. E.
- Affiliations
- University College London (GB)
- Imperial College London (GB)
- Corresponding author
- Futter, Clare E.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- Volume
- 127
- Issue
- Pt 17
- Pages
- 3852-61
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC4150067
- OpenAlex
- W2014852513
- Cited by
- 60
- References
- 57
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 11 · 2023: 11 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 8 · 2017: 3 · 2016: 1 · 2015: 6
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cell Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust (093445)
- Imperial College London
- Directorate for Biological Sciences
- Medical Research Council (P13251)
- Biotechnology and Biological Sciences Research Council (BB/D526953)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- phagosome maturation, retinal pigment epithelium, rod outer segment phagocytosis, phagosome-lysosome fusion, cathepsin D, lysosomes, protease sensitivity, retinal aging, macrophages
- MeSH terms
- Animals, Cell Separation, Lysosomes, Macrophages, Mice, Inbred C57BL, Phagocytosis, Phagosomes, Endosomes, Rhodopsin, Retinal Pigment Epithelium
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