Characterization of cell type-specific endocannabinoid signaling at biochemical and behavioral level

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Multi-protein complexes can constitute regulatory signaling units, which are able to integrate and modify a multitude of different signals received by the cell from extracellular and/or intracellular sources. Proteins with high numbers of functional connections are called “hub proteins” and are particularly interesting as central regulators and integrators of cellular processes, including synaptic plasticity, cell division, and cell differentiation. The endocannabinoid system (ECS) represents a widespread signaling system, both in the nervous system, but also in non-neuronal cell types. In this proposal, we aim at identifying multi-protein complexes formed by the CB1 receptor. We will employ the so-called tandem affinity purification (TAP) method, allowing the isolation of native protein complexes with subsequent protein sequence determination by MALDI-TOF. In extension to previous work, we aim at allocating CB1 receptor functions to the serotonergic system, combining behavioral, electrophysiological and the biochemical methods. By comparing CB1 receptor function in three different neurotransmitter systems (glutamatergic, GABAergic, serotonergic system), these experiments should shed novel light onto cell type-specific CB1 receptor signaling processes.