Valeria L. Robleto, Ya Zhuo, Joseph M. Crecelius, Sara Benzow, Adriano Marchese
{"title":"SNX9 家族介导不依赖于βarrestin 的 GPCR 内吞。","authors":"Valeria L. Robleto, Ya Zhuo, Joseph M. Crecelius, Sara Benzow, Adriano Marchese","doi":"10.1038/s42003-024-07157-7","DOIUrl":null,"url":null,"abstract":"Agonist-stimulated GPCR endocytosis typically occurs via the multi-faceted adaptor proteins known as βarrestins. However, endocytosis of several GPCRs occurs independently of β-arrestins, suggesting an additional mode of GPCR endocytosis, but the mechanisms remain unknown. Here we provide evidence that sorting nexin 9 (SNX9), a previously described endocytic remodeling protein, functions as a novel cargo adaptor that promotes agonist-stimulated GPCR endocytosis. We show that SNX9 and SNX18, but not β-arrestins, are necessary for endocytosis of the chemokine receptor CXCR4. SNX9 is recruited to CXCR4 at the plasma membrane and interacts directly with the carboxyl-terminal tail of the receptor in a phosphorylation-dependent manner. We also provide evidence that some receptors do not require SNX9 and SNX18 nor β-arrestins for endocytosis, suggesting additional modes for GPCR endocytosis. These results provide novel insights into the mechanisms regulating GPCR trafficking and broaden our overall understanding of GPCR regulation. Research sheds light on mechanisms governing βarrestin-independent endocytosis of GPCRs.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":"1-13"},"PeriodicalIF":5.2000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544122/pdf/","citationCount":"0","resultStr":"{\"title\":\"SNX9 family mediates βarrestin-independent GPCR endocytosis\",\"authors\":\"Valeria L. Robleto, Ya Zhuo, Joseph M. Crecelius, Sara Benzow, Adriano Marchese\",\"doi\":\"10.1038/s42003-024-07157-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Agonist-stimulated GPCR endocytosis typically occurs via the multi-faceted adaptor proteins known as βarrestins. However, endocytosis of several GPCRs occurs independently of β-arrestins, suggesting an additional mode of GPCR endocytosis, but the mechanisms remain unknown. Here we provide evidence that sorting nexin 9 (SNX9), a previously described endocytic remodeling protein, functions as a novel cargo adaptor that promotes agonist-stimulated GPCR endocytosis. We show that SNX9 and SNX18, but not β-arrestins, are necessary for endocytosis of the chemokine receptor CXCR4. SNX9 is recruited to CXCR4 at the plasma membrane and interacts directly with the carboxyl-terminal tail of the receptor in a phosphorylation-dependent manner. We also provide evidence that some receptors do not require SNX9 and SNX18 nor β-arrestins for endocytosis, suggesting additional modes for GPCR endocytosis. These results provide novel insights into the mechanisms regulating GPCR trafficking and broaden our overall understanding of GPCR regulation. Research sheds light on mechanisms governing βarrestin-independent endocytosis of GPCRs.\",\"PeriodicalId\":10552,\"journal\":{\"name\":\"Communications Biology\",\"volume\":\" \",\"pages\":\"1-13\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544122/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Communications Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s42003-024-07157-7\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Communications Biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s42003-024-07157-7","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
SNX9 family mediates βarrestin-independent GPCR endocytosis
Agonist-stimulated GPCR endocytosis typically occurs via the multi-faceted adaptor proteins known as βarrestins. However, endocytosis of several GPCRs occurs independently of β-arrestins, suggesting an additional mode of GPCR endocytosis, but the mechanisms remain unknown. Here we provide evidence that sorting nexin 9 (SNX9), a previously described endocytic remodeling protein, functions as a novel cargo adaptor that promotes agonist-stimulated GPCR endocytosis. We show that SNX9 and SNX18, but not β-arrestins, are necessary for endocytosis of the chemokine receptor CXCR4. SNX9 is recruited to CXCR4 at the plasma membrane and interacts directly with the carboxyl-terminal tail of the receptor in a phosphorylation-dependent manner. We also provide evidence that some receptors do not require SNX9 and SNX18 nor β-arrestins for endocytosis, suggesting additional modes for GPCR endocytosis. These results provide novel insights into the mechanisms regulating GPCR trafficking and broaden our overall understanding of GPCR regulation. Research sheds light on mechanisms governing βarrestin-independent endocytosis of GPCRs.
期刊介绍:
Communications Biology is an open access journal from Nature Research publishing high-quality research, reviews and commentary in all areas of the biological sciences. Research papers published by the journal represent significant advances bringing new biological insight to a specialized area of research.