CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments
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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments ; day:07 ; month:10 ; year:2024 ; extent:15
Advanced science ; (07.10.2024) (gesamt 15)
- Creator
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Yang, Song
Yu, Fan
Yang, Mulin
Ni, Hua
Bu, Weiwen
Yin, Hanxiao
Yang, Jia
Wang, Weishu
Zhai, Denghui
Wu, Xuemei
Ma, Nan
Li, Te
Hao, Huijie
Ran, Jie
Song, Ting
Li, Dengwen
Yoshida, Sei
Lu, Quanlong
Yang, Yunfan
Zhou, Jun
Liu, Min
- DOI
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10.1002/advs.202404067
- URN
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urn:nbn:de:101:1-2410081404422.009331561703
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:31 AM CEST
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Associated
- Yang, Song
- Yu, Fan
- Yang, Mulin
- Ni, Hua
- Bu, Weiwen
- Yin, Hanxiao
- Yang, Jia
- Wang, Weishu
- Zhai, Denghui
- Wu, Xuemei
- Ma, Nan
- Li, Te
- Hao, Huijie
- Ran, Jie
- Song, Ting
- Li, Dengwen
- Yoshida, Sei
- Lu, Quanlong
- Yang, Yunfan
- Zhou, Jun
- Liu, Min
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