Molecular Systems Biology (May 2025)
The solute carrier superfamily interactome
- 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
Affiliations
- Fabian Frommelt
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Rene Ladurner
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Ulrich Goldmann
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Gernot Wolf
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Alvaro Ingles-Prieto
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Eva Lineiro-Retes
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Zuzana Gelová
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Ann-Katrin Hopp
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Eirini Christodoulaki
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Shao Thing Teoh
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Philipp Leippe
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Brianda L Santini
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Manuele Rebsamen
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Sabrina Lindinger
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Iciar Serrano
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Svenja Onstein
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Christoph Klimek
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Barbara Barbosa
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Anastasiia Pantielieieva
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Vojtech Dvorak
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Thomas J Hannich
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Julian Schoenbett
- Novartis Pharma AG, Novartis Biomedical Research NBR/DSc
- Gilles Sansig
- Novartis Pharma AG, Novartis Biomedical Research NBR/DSc
- Tamara A M Mocking
- Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University
- Jasper F Ooms
- Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University
- Adriaan P IJzerman
- Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University
- Laura H Heitman
- Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University
- Peter Sykacek
- Department of Biotechnology, University of Natural Resources and Life Sciences
- Juergen Reinhardt
- Novartis Pharma AG, Novartis Biomedical Research NBR/DSc
- André C Müller
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Tabea Wiedmer
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Giulio Superti-Furga
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- DOI
- https://doi.org/10.1038/s44320-025-00109-1
- Journal volume & issue
-
Vol. 21,
no. 6
pp. 632 – 675
Abstract
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.
Keywords