Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level
| Autor: | Noushafarin Khajavi, Gunnar Kleinau, Denise Zwanziger, Maren Rehders, Jana Fischer, Catherine L. Worth, Anne Müller, Heike Biebermann, Burkhard Wiesner, Dagmar Führer, Claudia Rutz, Ralf Schülein, Heiko Krude, Klaudia Brix |
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| Rok vydání: | 2017 |
| Předmět: |
Monocarboxylic Acid Transporters
0301 basic medicine endocrine system endocrine system diseases Medizin Thyroid Gland Gene Expression Thyrotropin receptor 03 medical and health sciences Cellular and Molecular Neuroscience Chlorocebus aethiops Animals Humans Protein Interaction Maps Receptor Molecular Biology Integral membrane protein G protein-coupled receptor Pharmacology Monocarboxylate transporter Symporters biology Chemistry Receptors Thyrotropin Transporter Cell Biology Basolateral plasma membrane Major facilitator superfamily Cell biology HEK293 Cells 030104 developmental biology COS Cells biology.protein Molecular Medicine Protein Multimerization hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Cellular and Molecular Life Sciences. 75:2227-2239 |
| ISSN: | 1420-9071 1420-682X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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