Interactions between G-protein Coupled Receptors and Ligand Gated Ion Channels (GPCR-LGIC COUPLING)

2014-9-30
Dopamine receptors are members of G-protein coupled receptor superfamily. These receptors are the key point of dopaminergic system, which controls the regulation of memory, attention, food intake, endocrine regulation, psychomotor activity and positive reinforcement. To regulate so many critically important neurological events, dopamine receptors have complex interactions with other receptors and ion channels. In this study, a trimeric complex comprising D2 receptor -which is a subtype of dopamine receptors- , A2A adenosine receptor being another G-protein coupled receptor and a ligand gated ion channel N-methyl-D-aspartate (NMDA) receptor will be investigated. The aim of this project will be the application of a novel technique we refer as SplitGFP-FRET for the first time. For this study, “Fluorescence Resonance Energy Transfer” and “Split GFP” methods will be combined so as to reveal the trimeric D2 dopamine receptor- A2A adenosine receptor-NMDA receptor interactions. With the proposed study, a fluorescence technique to analyze live cell culture will be developed. This model will potentially lead to understanding of molecular mechanisms of many neuropathological conditions like schizophrenia and Parkinson’s disease because these disorders have already been shown to be associated with dysregulations in dopaminergic systems. Therefore, this project aims to reveal detailed links between schizophrenia and interactions of D2 dopamine receptor with other receptors and ion channels. The developed live cell model will also be useful for testing anti-psychotic drugs whether they have effects on disruption of protein-protein interactions, which will, in turn, ease screening of newly designed drugs.

Suggestions

INVESTIGATION OF PHYSICAL INTERACTION BETWEEN Gαi AND Gαs PROTEINS VIA FRET IN LIVE CELLS
Balkan, Seyda Tuğçe; Son, Çağdaş Devrim; Küçük Baloğlu, Fatma; Department of Biochemistry (2021-8-11)
GPCR’s are seven-transmembrane receptors that transmit external signals to the intracellular environment via secondary messenger systems through heterotrimeric G proteins. Heterotrimeric G proteins consist of α and β-γ subunits. Until recent years, scientists thought that GPCR signal transduction occurs between one GPCR and one heterotrimeric G protein; however, recently, it has been shown that GPCR’s can make oligomers. Oligomerization of GPCR allows cells to tune the intensity of the signal and respond ap...
Visualization of interactions between fluorescently tagged g protein α11, α12/13 subtypes and adenosine 2a, dopamine 2 or homodimer adenosine 2a/2a receptors
Kostromin, İrmak Begüm; Son, Çağdaş Devrim; Department of Biology (2018)
G-Protein-coupled receptors (GPCRs) belong to one of the largest family of cell surface receptors, which transmit extracellular signals to intracellular responses by interacting with G- proteins. The G proteins are known as molecular switches that regulates different pathways via control of secondary messengers and signaling proteins. Adenosine 2A (A2A) and Dopamine 2 (D2) receptors belong to G-Protein-coupled receptors (GPCRs) family and are located mostly in striatopallidal γ-aminobutyric acid (GABA) cont...
Optimization of internal tagging of inhibitory G-proteins for investigating their interactions with dopamine receptor D2 via fret method
Özcan, Gizem; Son, Çağdaş Devrim; Özçubukçu, Salih; Department of Biochemistry (2016)
G-Protein Coupled Receptors (GPCRs) constitute a large family of receptors which act by sensing the molecules outside the cell and start a signal transduction inside the cell through interacting with their associated G-proteins. This interaction results in activation or repression of related signaling pathways via associated secondary messengers. Dopamine receptor D2 (D2R) is a member of D2-like Dopamine Receptor group, which also belongs to the GPCR family. It is known that D2R has critical roles in emotio...
Prediction of transmembrane regions of g protein-coupled receptors using machine learning techniques
Çınar, Muazzez Çelebi; Son, Çağdaş Devrim; Department of Molecular Biology and Genetics (2019)
G protein-coupled receptors (GPCRs) are one of the largest and the most significant membrane receptor families in eukaryotes. They transmit extracellular stimuli to the inside of the cell by undergoing conformational changes. GPCRs can recognize a diversity of extracellular ligands including hormones, neurotransmitters, odorants, photons, and ions. These receptors are associated with a variety of diseases in humans such as cancer and central nervous system disorders, and can be proclaimed as one of the most...
Comparison of fluorescent protein labelled and wild type NMDA receptor distribution
Pirinçci, Şerife Şeyda; Son, Çağdaş Devrim; Department of Biology (2013)
NMDA (N-methyl D-aspartate) Receptor is a ligand and voltage gated ion channel and involved in many processes such as synaptic plasticity, memory formation, behavioral responses and cell survival. In the sense of functional activity, cellular localization of NMDAR is important since this receptor shows its activity on the membrane. Although NMDA receptor is intensely studied there are no satisfying study showing its localization with microscobic methods. Besides, the effect of florescent protein labelling o...
Citation Formats
Ç. D. Son, “Interactions between G-protein Coupled Receptors and Ligand Gated Ion Channels (GPCR-LGIC COUPLING),” 2014. Accessed: 00, 2020. [Online]. Available: https://cordis.europa.eu/project/id/268336.