Light‐responsive microRNA miR‐211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance
Open accessAbstract
Vertebrate vision relies on the daily phagocytosis and lysosomal degradation of photoreceptor outer segments (POS) within the retinal pigment epithelium (RPE). However, how these events are controlled by light is largely unknown. Here, we show that the light-responsive miR-211 controls lysosomal biogenesis at the beginning of light-dark transitions in the RPE by targeting Ezrin, a cytoskeleton-associated protein essential for the regulation of calcium homeostasis. miR-211-mediated down-regulation of Ezrin leads to Ca 2+ influx resulting in the activation of calcineurin, which in turn activates TFEB, the master regulator of lysosomal biogenesis. Light-mediated induction of lysosomal biogenesis and function is impaired in the RPE from miR-211-/- mice that show severely compromised vision. Pharmacological restoration of lysosomal biogenesis through Ezrin inhibition rescued the miR-211-/- phenotype, pointing to a new therapeutic target to counteract retinal degeneration associated with lysosomal dysfunction.
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Lack of miR-211 upregulates ezrin, causing defective lysosomal biogenesis and degradative capacity, whereas its upregulation increases lysosome number and stimulates fusion with phagosomes.
“Lack of miR-211 also results in upregulation of ezrin and subsequent defective lysosomal biogenesis and degradative capacity. On the other hand, its upregulation results in increased lysosome number and stimulates their fusion with phagosomes [270].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [270]
The sections ‘miR-211 controls autophagic flux in vitro’ and ‘Ezrin overexpression suppresses lysosomal biogenesis and function in vitro’ support the link between miR-211 loss, increased Ezrin, and impaired lysosomal biogenesis and degradative function. The former section also reports more lysosomes after miR-211 overexpression, but specifically finds increased fusion of lysosomes with autophagosomes, not phagosomes. (LLM, conf=0.88)
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Cites
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“Culturing ARPE-19 cells in the presence of NSC668394 led to a significant increase in the number of lysosomes and upregulated lysosomal markers, as demonstrated by immunofluorescence (Fig 3A and B (Kimura et al , 2007; Settembre et al , 2011).”
Noncanonical autophagy promotes the visual cycle
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Small molecule inhibitors of ezrin inhibit the invasive phenotype of osteosarcoma cells
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Protective responses to sublytic complement in the retinal pigment epithelium
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Research works printed but not linked: 2
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MicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Naso, F., Intartaglia, D., Falanga, D., Soldati, C., Polishchuk, E., Giamundo, G., Tiberi, P., Marrocco, E., Scudieri, P., Di Malta, C., Trapani, I., Nusco, E., Salierno, F. G., Surace, E. M., Galietta, L. J., Banfi, S., Auricchio, A., Ballabio, A., Medina, D. L., & Conte, I.
- Affiliations
- Telethon Institute Of Genetics And Medicine (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Baylor College of Medicine (US)
- ORCID
- Venue
- The EMBO Journal
- Published
- 2020-03-10
- Volume
- 39
- Issue
- 8
- Pages
- e102468-e102468
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC7156966
- OpenAlex
- W3011571820
- Cited by
- 46
- References
- 7
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 1
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- Fondazione Telethon (TMICCBX16TT, TGM16CB6)
- European Research Council (311682, 694282)
- BrightFocus Foundation (M2015317)
- National Institutes of Health (R01‐NS078072)
- Huffington Foundation
- Associazione Italiana per la Ricerca sul Cancro (21052, 22103)
- Ministerio dell'Istruzione, dell'Universita e della Ricerca (RBAP11Z3YA)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- miR-211, ezrin, lysosomal biogenesis, retinal pigment epithelium, photoreceptor outer segment phagocytosis, calcineurin, TFEB, calcium influx, light-dark cycle, retinal degeneration, microRNA, lysosomal dysfunction
- MeSH terms
- Ezrin, Animals, Autophagy, Calcium, Cytoskeletal Proteins, Gene Expression Regulation, Light, Lysosomes, Phagocytosis, Phagosomes, Down-Regulation, Mice, Knockout, MicroRNAs, Mice, Retinal Pigment Epithelium
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