Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy.
Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy.
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细胞因子信号传导抑制剂 2 通过增强自噬调节视网膜色素上皮代谢
DOI：
10.3389/fnins.2021.738022
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发表时间：
2021
影响因子：
4.3
通讯作者：
Chi ZL
中科院分区：
文献类型：
--
作者：
Liu XY;Lu R;Chen J;Wang J;Qian HM;Chen G;Wu RH;Chi ZL
Retinal pigment epithelium (RPE) serves critical functions in maintaining retinal homeostasis. An important function of RPE is to degrade the photoreceptor outer segment fragments daily to maintain photoreceptor function and longevity throughout life. An impairment of RPE functions such as metabolic regulation leads to the development of age-related macular degeneration (AMD) and inherited retinal degenerative diseases. As substrate recognition subunit of a ubiquitin ligase complex, suppressor of cytokine signaling 2 (SOCS2) specifically binds to the substrates for ubiquitination and negatively regulates growth hormone signaling. Herein, we explore the role of SOCS2 in the metabolic regulation of autophagy in the RPE cells. SOCS2 knockout mice exhibited the irregular morphological deposits between the RPE and Bruch’s membrane. Both in vivo and in vitro experiments showed that RPE cells lacking SOCS2 displayed impaired autophagy, which could be recovered by re-expressing SOCS2. SOCS2 recognizes the ubiquitylated proteins and participates in the formation of autolysosome by binding with autophagy receptors and lysosome-associated membrane protein2 (LAMP-2), thereby regulating the phosphorylation of glycogen synthase kinase 3β (GSK3β) and mammalian target of rapamycin (mTOR) during the autophagy process. Our results imply that SOCS2 participates in ubiquitin-autophagy-lysosomal pathway and enhances autophagy by regulating GSK3β and mTOR. This study provides a potential therapeutic target for AMD.
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影响因子：
16.2
作者：
Giaime E;Tong Y;Wagner LK;Yuan Y;Huang G;Shen J
通讯作者：
Shen J
影响因子：
16
作者：
Duran A;Amanchy R;Linares JF;Joshi J;Abu-Baker S;Porollo A;Hansen M;Moscat J;Diaz-Meco MT
通讯作者：
Diaz-Meco MT
影响因子：
64.5
作者：
Kim JY;Zhao H;Martinez J;Doggett TA;Kolesnikov AV;Tang PH;Ablonczy Z;Chan CC;Zhou Z;Green DR;Ferguson TA
通讯作者：
Ferguson TA
影响因子：
--
作者：
Abokyi, Samuel;Shan, Sze Wan;Tse, Dennis Yan-yin
通讯作者：
Tse, Dennis Yan-yin
影响因子：
16
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje