ArticleThe Journal of biological chemistry2016
Regulation of Phagolysosomal Digestion by Caveolin-1 of the Retinal Pigment Epithelium Is Essential for Vision.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Is Caveolin-1 Required for Retinal Neuroprotection?Advances in experimental medicine and biology · 2025Review
- Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Clearance phagocytosis by the retinal pigment epithelial during photoreceptor outer segment renewal: Molecular mechanisms and relation to retinal inflammation.Immunological reviews · 2023Review
- Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration inScience advances · 2023Article
- A novel quantification method for retinal pigment epithelium phagocytosis using a very-long-chain polyunsaturated fatty acids-based strategy.Frontiers in molecular neuroscience · 2023Article
- Caveolin-1 in vascular health and glaucoma: A critical vascular regulator and potential therapeutic target.Frontiers in medicine · 2023Review
- Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors.Frontiers in immunology · 2023Article
- Redox Regulation of Signaling Complex between Caveolin-1 and Neuronal Calcium Sensor Recoverin.Biomolecules · 2022Article
- Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease.Progress in retinal and eye research · 2022Review
- Regulation of the rhythmic diversity of daily photoreceptor outer segment phagocytosis in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Differences in Diurnal Rhythm of Rod Outer Segment Renewal between 129T2/SvEmsJ and C57BL/6J Mice.International journal of molecular sciences · 2022Article
- Proteins Associated with Phagocytosis Alteration in Retinal Pigment Epithelial Cells Derived from Age-Related Macular Degeneration Patients.Antioxidants (Basel, Switzerland) · 2022Article
- Probing Photoreceptor Outer Segment Phagocytosis by the RPE In Vivo: Models and Methodologies.International journal of molecular sciences · 2022Review
- Caveolin-1 Down-Regulation Reduces VEGF-A Secretion Induced by IGF-1 in ARPE-19 Cells.Life (Basel, Switzerland) · 2021Article
- Proposed therapy, developed in aeLife · 2021Article
- Article
- Glucocorticoid-mediated induction of caveolin-1 disrupts cytoskeletal organization, inhibits cell migration and re-epithelialization of non-healing wounds.Communications biology · 2021Article
- Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.Investigative ophthalmology & visual science · 2020Article
- Caveolin-1 Ablation Imparts Partial Protection Against Inner Retinal Injury in Experimental Glaucoma and Reduces Apoptotic Activation.Molecular neurobiology · 2020Article
- Physiologic Consequences of Caveolin-1 Ablation in Conventional Outflow Endothelia.Investigative ophthalmology & visual science · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Caveolin-1 associates with the endo/lysosomal machinery of cells in culture, suggesting that it functions at these organelles independently of its contribution to cell surface caveolae. Here we explored mice lacking caveolin-1 specifically in the retinal pigment epithelium (RPE). The RPE supports neighboring photoreceptors via diurnal phagocytosis of spent photoreceptor outer segment fragments. Like mice lacking caveolin-1 globally, (RPE)CAV1(-/-) mice developed a normal RPE and neural retina but showed reduced rod photoreceptor light responses, indicating that lack of caveolin-1 affects photoreceptor function in a non-cell-autonomous manner. (RPE)CAV1(-/-) RPE in situ showed normal particle engulfment but delayed phagosome clearance and reversed diurnal profiles of levels and activities of lysosomal enzymes. Therefore, eliminating caveolin-1 specifically impairs phagolysosomal degradation by the RPE in vivo. Endogenous caveolin-1 was recruited to maturing phagolysosomes in RPE cells in culture. Consistent with these in vivo data, a moderate increase (to ∼ 2.5-fold) or decrease (by half) of caveolin-1 protein levels in RPE cells in culture was sufficient to accelerate or impair phagolysosomal digestion, respectively. A mutant form of caveolin-1 that fails to reach the cell surface augmented degradation like wild-type caveolin-1. Acidic lysosomal pH and increased protease activity are essential for digestion. We show that halving caveolin-1 protein levels significantly alkalinized lysosomal pH and decreased lysosomal enzyme activities. Taken together, our results reveal a novel role for intracellular caveolin-1 in modulating phagolysosomal function. Moreover, they show, for the first time, that organellar caveolin-1 significantly affects tissue functionality in vivo.
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Registered trials
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