CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments

Autor: Song Yang, Fan Yu, Mulin Yang, Hua Ni, Weiwen Bu, Hanxiao Yin, Jia Yang, Weishu Wang, Denghui Zhai, Xuemei Wu, Nan Ma, Te Li, Huijie Hao, Jie Ran, Ting Song, Dengwen Li, Sei Yoshida, Quanlong Lu, Yunfan Yang, Jun Zhou, Min Liu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 45, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
20240406
DOI: 10.1002/advs.202404067
Popis: 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.
Databáze: Directory of Open Access Journals
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