ArticleAutophagy2017
RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Retinal Pigment Epithelium Phagocytosis and Retinal Degenerative Diseases.Aging and disease · 2025Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Role and regulation of kinases in age-related macular degeneration.Journal of translational medicine · 2026Review
- ADORA2A activation restores lysosomal function and photoreceptor outer segment degradation in stressed retinal pigment epithelium.Frontiers in physiology · 2026Article
- Article
- Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.International journal of molecular sciences · 2025Review
- Roles of class III phosphatidylinositol 3-kinase, Vps34, in phagocytosis, autophagy, and endocytosis in retinal pigmented epithelium.iScience · 2025Article
- Ezrin defines TSC complex activation at endosomal compartments through EGFR-AKT signaling.eLife · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.Autophagy reports · 2025Review
- Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis.Inflammation · 2024Article
- The murine retinal pigment epithelium requires peroxisomal β-oxidation to maintain lysosomal function and prevent dedifferentiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- mTORC1 Signaling and Negative Lens-Induced Axial Elongation.Investigative ophthalmology & visual science · 2023Article
- Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2023Review
- LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models.Nature communications · 2023Article
- The Essential Role of Light-Induced Autophagy in the Inner Choroid/Outer Retinal Neurovascular Unit in Baseline Conditions and Degeneration.International journal of molecular sciences · 2023Review
- AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.Autophagy reports · 2023Article
- Human intestinal epithelial cells can internalize luminal fungiFrontiers in immunology · 2023Article
- Autophagy Induced by Toll-like Receptor Ligands Regulates Antigen Extraction and Presentation by B Cells.Cells · 2022Article
- LC3-associated endocytosis and the functions of Rubicon and ATG16L1.Science advances · 2022Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions. Our data reveal that RPE cells promote LAP through the expression of RUBCN/Rubicon (RUN domain and cysteine-rich domain containing Beclin 1-interacting protein) and suppress autophagy through the activation of EGFR (epidermal growth factor receptor). In the morning when photoreceptor outer segments (POS) phagocytosis and LAP are highest, RUBCN expression is increased. At the same time, outer segment phagocytosis activates the EGFR resulting in MTOR (mechanistic target of rapamycin [serine/threonine kinase]) stimulation, the accumulation of SQSTM1/p62, and the phosphorylation of BECN1 (Beclin 1, autophagy related) on an inhibitory residue thereby suppressing autophagy. Silencing Rubcn, preventing EGFR activity or directly inducing autophagy in RPE cells by starvation inhibits phagocytic degradation of POS. Thus, RPE cells regulate lysosomal pathways during the critical period of POS phagocytosis to support retinal homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.