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P 20 - Dr. Uwe Schulte
The molecular basis of the diversity and functional specificity of neuronal metabotropic glutamate receptor-mediated signaling
| Dr. Uwe Schulte Physiologisches Institut II Hermann-Herder-Str. 7 79104 Freiburg Phone: + 49 761 203-5163 Fax: +49 761 203-5163 |
Project Summary
Metabotropic glutamate receptors (mGluRs) are key modulators of synaptic transmission in the nervous system by controlling a variety of effectors and second messenger pathways. The specific molecular links to these pathways, however, have so far remained largely unresolved. We have used in-depth functional and quantitative proteomic analysis to unravel the subunit composition of native mGluRs and identified a set of largely novel interacting proteins for mGluR1 and 5. These were found to co-localize in distinct types and membrane domains ofneurons and include effectors, linkers to signaling pathways and proteins defining the local specificity of these links in a subtype-specific manner. Our future studies will focus on the functional implications of these interacting proteins. Specifically, we aim to (i) address the significance of mGluR heteromer formation and receptor stoichiometry with respect to quantitative tissue distribution, synaptic localization and coupling specificity to signaling pathways, (ii) investigate the role of identified proteins for neuronal targeting and formation of mGluR signaling domains and their effect on local and functional specificity of mGluR signaling, and (iii) study the impact of mGluRs on new effector proteins and their dependence on specific subtypes. To achieve these goals, we will combine quantitative microproteomic analyses, biochemical and cellular assays, high-resolution electron and fluorescence-based microscopy, imaging of Ca2+ and other second messengers, as well as electrophysiological recordings of mGluR responses in wildtype, targeted knockout or otherwise recombinantly modified brain tissues or neurons. | |
