Recent studies demonstrate that there are several G-protein coupled receptors
(GPCRs) that dimerize with other GPCRs and form heterodimers. Adenosine
A2A-Dopamine D2 receptor interaction is one of the examples for GPCR
heterodimerization. Both receptors bear critical roles in physiological processes.
Adenosine A2A receptor has functions in neurotransmission, cardiovascular
system and immune response. On the other hand, dopamine receptors are the
key point of dopaminergic system, which controls the regulation of memory,
attention, food intake, endocrine regulation, psychomotor activity and positive
reinforcement. Deregulation in dopamine signaling could cause neurological
disorders such as Parkinson&rsquo / s disease and schizophrenia. Dopamine D2R and
adenosine A2AR have been shown to interact in striatum and modulate
dopaminergic activity.
The purpose of this study is to optimize Fluorescence Resonance Energy
Transfer (FRET) method to detect dimerization of D2R and A2AR by tagging
them with EGFP (enhanced green fluorescent protein) and mCherry (a red
fluorescent protein) in live N2a cell line using laser scanning confocal
microscope. Establishing this model will pave the ways for understanding
mechanisms of interaction between dopamine and adenosine signaling, thereby,
contributing to the understanding molecular mechanisms of some
neurophysiological events and disorders. Moreover, the fluorescence based live
cell model will be used to detect effects of potential anti-psychotic drugs on the
interaction of these two receptors.
Indeed, follow-up studies are necessary to extend the limits of this project.
Further imaging analyses and drug-receptor interaction studies can be readily
applied to extract more information on dopamine-adenosine signaling by using
the system developed with this thesis study.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12613365/index.pdf |
| Date | 01 July 2011 |
| Creators | Unlu, Gokhan |
| Contributors | Son, Cagdas D |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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