The solute carrier superfamily interactome.
| Title: | The solute carrier superfamily interactome. |
|---|---|
| Authors: | Frommelt F; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Ladurner R; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Goldmann U; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Wolf G; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Ingles-Prieto A; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Lineiro-Retes E; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Gelová Z; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Hopp AK; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Christodoulaki E; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Teoh ST; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Leippe P; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Santini BL; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Rebsamen M; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Lindinger S; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Serrano I; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Onstein S; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Klimek C; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Barbosa B; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Pantielieieva A; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Dvorak V; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Hannich TJ; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Schoenbett J; Novartis Pharma AG, Novartis Biomedical Research NBR/DSc, CH-4002, Basel, Switzerland.; Sansig G; Novartis Pharma AG, Novartis Biomedical Research NBR/DSc, CH-4002, Basel, Switzerland.; Mocking TAM; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Ooms JF; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; IJzerman AP; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Heitman LH; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Sykacek P; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190, Vienna, Austria.; Reinhardt J; Novartis Pharma AG, Novartis Biomedical Research NBR/DSc, CH-4002, Basel, Switzerland.; Müller AC; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Wiedmer T; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.; Superti-Furga G; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria. gsuperti@cemm.oeaw.ac.at.; Center for Physiology and Pharmacology, Medical University of Vienna, 1090, Vienna, Austria. gsuperti@cemm.oeaw.ac.at.; Fondazione Ri.MED, Palermo, Italy. gsuperti@cemm.oeaw.ac.at. |
| Source: | Molecular systems biology [Mol Syst Biol] 2025 Jun; Vol. 21 (6), pp. 632-675. Date of Electronic Publication: 2025 May 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: EMBO Press Country of Publication: Germany NLM ID: 101235389 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-4292 (Electronic) Linking ISSN: 17444292 NLM ISO Abbreviation: Mol Syst Biol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : Heidelberg : EMBO Press; Original Publication: London : Nature Pub. Group, c2005- |
| MeSH Terms: | Solute Carrier Proteins*/metabolism ; Solute Carrier Proteins*/genetics ; Membrane Transport Proteins*/metabolism ; Membrane Transport Proteins*/genetics; Proteomics/methods ; Protein Interaction Mapping/methods ; Humans ; Protein Interaction Maps ; Protein Binding ; Protein Transport ; HEK293 Cells |
| Abstract: | 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.; (© 2025. The Author(s).) |
| Competing Interests: | Disclosure and competing interests statement. GS-F is a co-founder and owns shares of Solgate GmbH, an SLC-focused company. |
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| Grant Information: | 777372 Innovative Medicines Initiative 2 |
| Contributed Indexing: | Keywords: AP-MS; Protein–protein Interactions; Proteostasis; SLC Superfamily; Trafficking |
| Substance Nomenclature: | 0 (Solute Carrier Proteins); 0 (Membrane Transport Proteins) |
| Entry Date(s): | Date Created: 20250512 Date Completed: 20250602 Latest Revision: 20250605 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12130317 |
| DOI: | 10.1038/s44320-025-00109-1 |
| PMID: | 40355756 |
| Database: | MEDLINE |
Journal Article