<i>O</i>-GlcNAcylation regulates phagocytosis by promoting Ezrin localization at the cell cortex

Song Yang; Hanyu Liu; Hua Ni; Lingyu Jiang; Mulin Yang; Quan Chen; Jun Zhou; Fan Yu

doi:10.1016/j.jgg.2023.02.003

Volume 50 Issue 7

Jul. 2023

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O-GlcNAcylation regulates phagocytosis by promoting Ezrin localization at the cell cortex

doi: 10.1016/j.jgg.2023.02.003

Song Yang^a,b,
Hanyu Liu^a,
Hua Ni^a,c,
Lingyu Jiang^a,
Mulin Yang^a,
Quan Chen^a,b,
Jun Zhou^a,b,
Fan Yu^a,b

a. State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin 300071, China;
b. CNBG-Nankai Joint Research Center, Nankai University, Tianjin 300071, China;
c. College of Life and Geographic Sciences, Kashi University, Xinjiang 844000, China

Funds:

The work was supported by grants from the National Natural Science Foundation of China (32100549 and 31991193).

Received Date: 2022-10-16
Accepted Date: 2023-02-02
Rev Recd Date: 2023-01-25
Publish Date: 2023-07-28

Abstract

Abstract

O-GlcNAcylation is a post-translational modification that serves as a cellular nutrient sensor and participates in multiple physiological and pathological processes. However, it remains uncertain whether O-GlcNAcylation is involved in the regulation of phagocytosis. Here, we demonstrate a rapid increase in protein O-GlcNAcylation in response to phagocytotic stimuli. Knockout of the O-GlcNAc transferase or pharmacological inhibition of O-GlcNAcylation dramatically blocks phagocytosis, resulting in the disruption of retinal structure and function. Mechanistic studies reveal that the O-GlcNAc transferase interacts with Ezrin, a membrane-cytoskeleton linker protein, to catalyze its O-GlcNAcylation. Our data further show that Ezrin O-GlcNAcylation promotes its localization to the cell cortex, thereby stimulating the membrane-cytoskeleton interaction needed for efficient phagocytosis. These findings identify a previously unrecognized role for protein O-GlcNAcylation in phagocytosis with important implications in both health and diseases.
- O-GlcNAcylation,
- Phagocytosis,
- Retinal pigment epithelium,
- Ezrin,
- Cytoskeleton

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References(52)

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