Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level |
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| Authors: | Jana Fischer Gunnar Kleinau Claudia Rutz Denise Zwanziger Noushafarin Khajavi Anne Müller Maren Rehders Klaudia Brix Catherine L Worth Dagmar Führer Heiko Krude Burkhard Wiesner Ralf Schülein Heike Biebermann |
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| Institution: | 1.Institut für Experimentelle P?diatrische Endokrinologie,Charité – Universit?tsmedizin Berlin,Berlin,Germany;2.Group Protein X-ray Crystallography and Signal Transduction, Institute of Medical Physics and Biophysics,Charité – Universit?tsmedizin Berlin,Berlin,Germany;3.Protein Trafficking Group,Leibniz-Forschungsinstitut für Molekulare Pharmakologie,Berlin,Germany;4.Division of Laboratory Research, Department of Endocrinology, Diabetology and Metabolism,University Hospital Essen, University Duisburg-Essen,Essen,Germany;5.Department of Life Sciences and Chemistry,Jacobs University Bremen,Bremen,Germany;6.Structural Bioinformatics and Protein Design Group,Leibniz-Forschungsinstitut für Molekulare Pharmakologie,Berlin,Germany;7.Cellular Imaging Group,Leibniz-Forschungsinstitut für Molekulare Pharmakologie,Berlin,Germany |
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| Abstract: | G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Indeed, we demonstrate strong interaction between both the proteins which causes a suppressed activation of Gq/11 by TSH-stimulated TSHR. Thus, we provide not only evidence for a novel interaction between the TSHR and MCT8, but could also prove this interaction on a single molecule level. Moreover, this interaction forces biased signaling at the TSHR. These results are of general interest for both the GPCR and the MFS research fields. |
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