Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy

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...

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Autores principales:	Xi-Yuan Liu, Rui Lu, Jing Chen, Jie Wang, Hong-Mei Qian, Gang Chen, Rong-Han Wu, Zai-Long Chi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	suppressor of cytokine signaling 2 retinal pigment epithelium autophagy ubiquitin glycogen synthase kinase (GSK)-3β mammalian target of rapamycin (mTOR) Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/14b84c31c08247c19efd035be8e087bf
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spelling	oai:doaj.org-article:14b84c31c08247c19efd035be8e087bf2021-11-08T05:50:42ZSuppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy1662-453X10.3389/fnins.2021.738022https://doaj.org/article/14b84c31c08247c19efd035be8e087bf2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.738022/fullhttps://doaj.org/toc/1662-453XRetinal 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.Xi-Yuan LiuRui LuJing ChenJie WangHong-Mei QianGang ChenRong-Han WuZai-Long ChiFrontiers Media S.A.articlesuppressor of cytokine signaling 2retinal pigment epitheliumautophagyubiquitinglycogen synthase kinase (GSK)-3βmammalian target of rapamycin (mTOR)Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	suppressor of cytokine signaling 2 retinal pigment epithelium autophagy ubiquitin glycogen synthase kinase (GSK)-3β mammalian target of rapamycin (mTOR) Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	suppressor of cytokine signaling 2 retinal pigment epithelium autophagy ubiquitin glycogen synthase kinase (GSK)-3β mammalian target of rapamycin (mTOR) Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Xi-Yuan Liu Rui Lu Jing Chen Jie Wang Hong-Mei Qian Gang Chen Rong-Han Wu Zai-Long Chi Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy
description	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.
format	article
author	Xi-Yuan Liu Rui Lu Jing Chen Jie Wang Hong-Mei Qian Gang Chen Rong-Han Wu Zai-Long Chi
author_facet	Xi-Yuan Liu Rui Lu Jing Chen Jie Wang Hong-Mei Qian Gang Chen Rong-Han Wu Zai-Long Chi
author_sort	Xi-Yuan Liu
title	Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy
title_short	Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy
title_full	Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy
title_fullStr	Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy
title_full_unstemmed	Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy
title_sort	suppressor of cytokine signaling 2 regulates retinal pigment epithelium metabolism by enhancing autophagy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/14b84c31c08247c19efd035be8e087bf
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_version_	1718442881669136384

Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy

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