Fabian Frommelt, Rene Ladurner, Ulrich Goldmann, Gernot Wolf, Alvaro Ingles-Prieto, Eva Lineiro-Retes, Zuzana Gelová, Ann-Katrin Hopp, Eirini Christodoulaki, Shao Thing Teoh, Philipp Leippe, Brianda L Santini, Manuele Rebsamen, Sabrina Lindinger, Iciar Serrano, Svenja Onstein, Christoph Klimek, Barbara Barbosa, Anastasiia Pantielieieva, Vojtech Dvorak, Thomas J Hannich, Julian Schoenbett, Gilles Sansig, Tamara A M Mocking, Jasper F Ooms, Adriaan P IJzerman, Laura H Heitman, Peter Sykacek, Juergen Reinhardt, André C Müller, Tabea Wiedmer, Giulio Superti-Furga
{"title":"溶质载体超族相互作用。","authors":"Fabian Frommelt, Rene Ladurner, Ulrich Goldmann, Gernot Wolf, Alvaro Ingles-Prieto, Eva Lineiro-Retes, Zuzana Gelová, Ann-Katrin Hopp, Eirini Christodoulaki, Shao Thing Teoh, Philipp Leippe, Brianda L Santini, Manuele Rebsamen, Sabrina Lindinger, Iciar Serrano, Svenja Onstein, Christoph Klimek, Barbara Barbosa, Anastasiia Pantielieieva, Vojtech Dvorak, Thomas J Hannich, Julian Schoenbett, Gilles Sansig, Tamara A M Mocking, Jasper F Ooms, Adriaan P IJzerman, Laura H Heitman, Peter Sykacek, Juergen Reinhardt, André C Müller, Tabea Wiedmer, Giulio Superti-Furga","doi":"10.1038/s44320-025-00109-1","DOIUrl":null,"url":null,"abstract":"<p><p>Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in a variety of subcellular membranes. Loss-of-function of an unusually high proportion of SLC transporters is genetically associated with a plethora of human diseases, making SLCs a rapidly emerging but challenging drug target class. Knowledge of their protein environment may elucidate the molecular basis for their functional integration with metabolic and cellular pathways and help conceive pharmacological interventions based on modulating proteostatic regulation. We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics. We employed a functional assessment based on RNA interference of interactors in combination with measurement of protein stability and localization. As an example, we detail the role of a SLC16A6 phospho-degron and the contributions of PDZ-domain proteins LIN7C and MPP1 to the trafficking of SLC43A2. Overall, our work offers a resource for SLC-protein interactions for the scientific community.</p>","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"632-675"},"PeriodicalIF":8.5000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130317/pdf/","citationCount":"0","resultStr":"{\"title\":\"The solute carrier superfamily interactome.\",\"authors\":\"Fabian Frommelt, Rene Ladurner, Ulrich Goldmann, Gernot Wolf, Alvaro Ingles-Prieto, Eva Lineiro-Retes, Zuzana Gelová, Ann-Katrin Hopp, Eirini Christodoulaki, Shao Thing Teoh, Philipp Leippe, Brianda L Santini, Manuele Rebsamen, Sabrina Lindinger, Iciar Serrano, Svenja Onstein, Christoph Klimek, Barbara Barbosa, Anastasiia Pantielieieva, Vojtech Dvorak, Thomas J Hannich, Julian Schoenbett, Gilles Sansig, Tamara A M Mocking, Jasper F Ooms, Adriaan P IJzerman, Laura H Heitman, Peter Sykacek, Juergen Reinhardt, André C Müller, Tabea Wiedmer, Giulio Superti-Furga\",\"doi\":\"10.1038/s44320-025-00109-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in a variety of subcellular membranes. Loss-of-function of an unusually high proportion of SLC transporters is genetically associated with a plethora of human diseases, making SLCs a rapidly emerging but challenging drug target class. Knowledge of their protein environment may elucidate the molecular basis for their functional integration with metabolic and cellular pathways and help conceive pharmacological interventions based on modulating proteostatic regulation. We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics. We employed a functional assessment based on RNA interference of interactors in combination with measurement of protein stability and localization. As an example, we detail the role of a SLC16A6 phospho-degron and the contributions of PDZ-domain proteins LIN7C and MPP1 to the trafficking of SLC43A2. Overall, our work offers a resource for SLC-protein interactions for the scientific community.</p>\",\"PeriodicalId\":18906,\"journal\":{\"name\":\"Molecular Systems Biology\",\"volume\":\" \",\"pages\":\"632-675\"},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130317/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Systems Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1038/s44320-025-00109-1\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Systems Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44320-025-00109-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in a variety of subcellular membranes. Loss-of-function of an unusually high proportion of SLC transporters is genetically associated with a plethora of human diseases, making SLCs a rapidly emerging but challenging drug target class. Knowledge of their protein environment may elucidate the molecular basis for their functional integration with metabolic and cellular pathways and help conceive pharmacological interventions based on modulating proteostatic regulation. We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics. We employed a functional assessment based on RNA interference of interactors in combination with measurement of protein stability and localization. As an example, we detail the role of a SLC16A6 phospho-degron and the contributions of PDZ-domain proteins LIN7C and MPP1 to the trafficking of SLC43A2. Overall, our work offers a resource for SLC-protein interactions for the scientific community.
期刊介绍：
Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems.
Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
