Multiplexed mapping of the interactome of GPCRs with receptor activity–modifying proteins-Reference-Cited by-同舟云学术

Multiplexed mapping of the interactome of GPCRs with receptor activity–modifying proteins

Published:2024-08-02 Issue:31 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Kotliar Ilana B.¹²^ORCID,Bendes Annika³^ORCID,Dahl Leo³^ORCID,Chen Yuanhuang¹²^ORCID,Saarinen Marcus⁴,Ceraudo Emilie¹^ORCID,Dodig-Crnković Tea³^ORCID,Uhlén Mathias³^ORCID,Svenningsson Per⁴⁵^ORCID,Schwenk Jochen M.³^ORCID,Sakmar Thomas P.¹⁶^ORCID

Affiliation:

1. Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY, USA.

2. Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA.

3. Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden.

4. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

5. Basal and Clinical Neuroscience, King’s College London, London, UK.

6. Department of Neurobiology, Care Sciences and Society, Section for Neurogeriatrics, Karolinska Institutet, Solna, Sweden.

Abstract

Receptor activity–modifying proteins (RAMPs) form complexes with G protein–coupled receptors (GPCRs) and may regulate their cellular trafficking and pharmacology. RAMP interactions have been identified for about 50 GPCRs, but only a few GPCR-RAMP complexes have been studied in detail. To elucidate a comprehensive GPCR-RAMP interactome, we created a library of 215 dual epitope-tagged (DuET) GPCRs representing all GPCR subfamilies and coexpressed each GPCR with each of the three RAMPs. Screening the GPCR-RAMP pairs with customized multiplexed suspension bead array (SBA) immunoassays, we identified 122 GPCRs that showed strong evidence for interaction with at least one RAMP. We screened for interactions in three cell lines and found 23 endogenously expressed GPCRs that formed complexes with RAMPs. Mapping the GPCR-RAMP interactome expands the current system-wide functional characterization of RAMP-interacting GPCRs to inform the design of selective therapeutics targeting GPCR-RAMP complexes.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.ado9959

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