title: Studies on the regulatory mechanisms of receptor - G protein complexes
reg no: ETF6492
project type: Estonian Science Foundation research grant
status: accepted
institution: University of Tartu
head of project: Ago Rinken
duration: 01.01.2005 - 31.12.2008
description: The aim of the project is to characterize regulatory mechanisms of formation of complexes between neurotransmitter receptors and G proteins. Better understanding of mechanisms of signal transduction via 7-TM receptors may open new possibilities for fine modulation of this system, which would be a target of new drugs or treatments. We'll use receptors of small ligands (muscarinic, dopaminergic, serotonergic) as well as receptors of peptides (melanocortin) as model systems in the project. The main attention will be paid on the role of receptors, RGS proteins, membranes and ions on the activation of G proteins and corresponding signal transduction. Within the project we plan to:
o study regulatory mechanisms of ligand and nucleotide binding to R-G complex. Determine the role of properties of membranes, receptor oligomerization and G protein regulators (RGS proteins) on the formation of the complex and signal transduction efficacy.
o study the influence of different ions on the ability α subunits of G proteins to bind nucleotides and interact with different subtypes of receptors. In addition to known Mg2+ binding site in the structure of Gi, we try to lokalize other Me2+-specific binding sites in structures of other G proteins and/or receptors, and determine their role in specific signal transduction systems.
o find regulatory mechanisms causing hypo- and hyperactivity of signal transduction of monoamine receptors in the brain in the case of different pathologies. We compare signal transduction systems of animals treated with 6-hydroxydopamine (animal model of Parkinson disease), parachloramphetamine, DSP-4 or other specific toxins and try to find biochemical nature of appeared differences.

project group
no name institution position  
1.Sergei KopantšukUniversity of TartuPh.D. student, researcher 
2.Sven ParkelUniversity of TartuPhD student 
3.Ago RinkenUniversity of Tartuprofessor 
4.Ain UustareUniversity of TartuResearch Associate 
5.Argo VonkUniversity of TartuPhD student