Research group Brunk
Main interests of our group are the functions of the Goa splice variants Go1alpha and Go2alpha in brain and the regulation of vesicular neurotransmitter transporters, especially VMAT2, by heterotrimeric G-proteins. Mechanisms underlying this regulation were identified by our group. Its physiological relevance was proven for the monoaminergic system. Furthermore we could show influence of Go2alpha on axonal growth.
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The efficacy of synaptic transmission shows short- and long-term variability. One factor which is assumed to contribute to the variability of transmission is the amount of neurotransmitter in synaptic vesicles. The filling of synaptic vesicles are performed by vesicular neurotransmitter transporters, such as the vesicular monoamine transporter 2 (VMAT2) in monoaminergic terminals. The activity of vesicular neurotransmitter transporters is in turn regulated by vesicle-associated heterotrimeric G-proteins. VMAT2 is controlled by the a-subunit of the heterotrimeric G-protein Go2 and the transporter appears to act like a G-protein coupled receptor. In fact, deletion of Go2alpha results in an imbalance of the dopaminergic system. Moreover, studies on Go1alpha deletion mutants indicate that Go2alpha and Go1alpha complementarily affect the monoaminergic system. This suggestion is further supported by the identification of interaction partners of constitutively active Go2alpha. Many of them also interact with Go1alpha in its active or inactive state.