ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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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
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Retinal Pigment Epithelium Phagocytosis and Retinal Degenerative Diseases.Aging and disease · 2025Pooled it
- The blood-retinal barrier in ocular pathologies: an updated narrative review.International ophthalmology · 2025Review
- Post-Translational Modifications in Cilia and Ciliopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- UFMylation Modulates OFIP Stability and Centrosomal Localization.Journal of clinical laboratory analysis · 2025Article
- CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Phagocytosis of shed photoreceptor outer segments by the retinal pigment epithelium (RPE) is essential for retinal homeostasis. Dysregulation of the phagocytotic process is associated with irreversible retinal degenerative diseases. However, the molecular mechanisms underlying the phagocytic activity of RPE cells remain elusive. In an effort to uncover proteins orchestrating retinal function, the cylindromatosis (CYLD) deubiquitinase is identified as a critical regulator of photoreceptor outer segment phagocytosis. CYLD-deficient mice exhibit abnormal retinal structure and function. Mechanistically, CYLD interacts with enkurin domain containing protein 1 (ENKD1) and deubiquitinates ENKD1 at lysine residues K141 and K242. Deubiquitinated ENKD1 interacts with Ezrin, a membrane-cytoskeleton linker, and stimulates the microvillar localization of Ezrin, which is essential for the phagocytic activity of RPE cells. These findings thus reveal a crucial role for the CYLD-ENKD1-Ezrin axis in regulating retinal homeostasis and may have important implications for the prevention and treatment of retinal degenerative diseases.
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Registered trials
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