The yeast Ste2p G protein-coupled receptor dimerizes on the cell plasma membrane

Cevheroglu, Orkun
Kumas, Gozde
Hauser, Melinda
Becker, Jeffrey M.
Son, Çağdaş Devrim
Dimerization of G protein-coupled receptors (GPCR) may play an important role in maturation, internalization, signaling and/or pharmacology of these receptors. However, the location where dimerization occurs is still under debate. In our study, variants of Ste2p, a yeast mating pheromone GPCR, were tagged with split EGFP (enhanced green fluorescent protein) fragments inserted between transmembrane domain seven and the C-terminus or appended to the C-terminus. Bimolecular Fluorescence Complementation (BiFC) assay was used to determine where receptor dimerization occurred during protein trafficking by monitoring generation of EGFP fluorescence, which occurred upon GPCR dimerization. Our results suggest that these tagged receptors traffic to the membrane as monomers, undergo dimerization or higher ordered oligomerization predominantly on the plasma membrane, and are internalized as dimers/oligomers. This study is the first to provide direct in vivo visualization of GPCR dimerization/oligomerization, during trafficking to and from the plasma membrane.


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Murat, Merve; Son, Çağdaş Devrim; Cevheroğlu, Orkun; Department of Molecular Biology and Genetics (2021-9-7)
G protein-coupled receptors (GPCRs) form oligomeric complexes in living cells, and these complex structures affect the receptor maturation, trafficking, and signaling processes. Adhesion G protein-coupled receptors (aGPCRs), the second-largest sub-family of GPCRs, interact with extracellular matrix and ligands on the adjacent cell surface to modulate tissue and organ development. However, it is still unclear whether aGPCRs interact with each other. In this study, ADGRG1 was used as a model aGPCR to investi...
The NF-kappa B target genes ICAM-1 and VCAM-1 are differentially regulated during spontaneous differentiation of Caco-2 cells
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Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cellcell and cellmicroenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line, which undergoes spontaneous re-differentiation when grown past confluency, we observed a loss of VCAM-1 (vascular cell adhesion molecule 1) mRNA expression, while ICAM-1 (intercellular cell adhesion m...
More than just a dimer: detection of G protein-coupled receptor oligomers using fluorescent protein reassembly of Ste2p, a yeast pheromone receptor
Cevheroğlu, Orkun; Son, Çağdaş Devrim; Akkaya, Mahinur S.; Department of Biotechnology (2015)
GPCRs are known to form homo- and hetero-dimers and this interaction could have important roles in internalization, maturation, function and/or pharmacology of these receptors. In the first part of the study bimolecular fluorescence complementation (BiFC) using split enhanced green fluorescent protein (EGFP) was used to determine the interaction and cellular location between various Ste2p constructs. Co-expression of two constructs, one with the N-terminus of EGFP inserted into the full-length receptor at t...
Detecting g-protein coupled receptor interactions using enhanced green fluorescent protein reassembly
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The largest class of cell surface receptors in mammalian genomes is the superfamily of G protein-coupled receptors (GPCRs) which are activated by a wide range of extracellular responses such as hormones, pheromones, odorants, and neurotransmitters. Drugs which have therapeutic effects on a wide range of diseases are act on GPCRs. In contrast to traditional idea, it is recently getting accepted that G-protein coupled receptors can form homo- and hetero-dimers and this interaction could have important role on...
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The classical GPCR signaling pathway, where a heterotrimeric G protein-GPCR interaction is sufficient to transmit the signal to effector proteins has been replaced by a heteromeric G protein-GPCR homo- or hetero-dimer interaction model over the past two decades. These studies demonstrate that GPCRs that interact with each other couple with a heteromeric G protein. In recent years, evidence suggests that dimer of GPCR dimers is required for some complex signal transductions. In these studies, it was proposed...
Citation Formats
O. Cevheroglu, G. Kumas, M. Hauser, J. M. Becker, and Ç. D. Son, “The yeast Ste2p G protein-coupled receptor dimerizes on the cell plasma membrane,” BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, pp. 698–711, 2017, Accessed: 00, 2020. [Online]. Available: