Role of beta arrestin 2 in neurotransmission

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G protein coupled receptors (GPCRs) represents the most important family of cell surface receptors involved in the regulation of neurotransmission. GPCRs are believed to regulate cell signaling trough activation of heterotrimeric G proteins. However, GPCRs have also been shown to exert their action through the formation of signaling complexes (signalomes) composed of signaling molecules and the scaffolding proteins beta-arrestins. We recently demonstrated that such a beta-arrestin signalome mediates some effects of dopamine receptor in vivo. Disruption of this complex in the mouse striatum results in a loss of regulation of signaling molecules Akt and GSK3 by dopamine and in reduced behavioral responses to dopaminergic drugs in mice lacking beta arrestin 2. The proposed research protocol has for objectives to examine further the regulation of Akt and GSK3 by beta-arrestin signaling complexes and to identify other neurotransmitter/receptor systems regulating the formation of beta-arrestin signaling complexes. This research will involve the use of different GPCR responding to neurotransmitters to evaluate the involvement of these receptors on the formation of beta-arrestin signaling complexes. Subsequently the physiological relevance of these findings will be evaluated in vivo using beta arrestin knockout mice. Beta-arrestin mediated signaling by GPCR may represent a general new mechanism of neurotransmission and a better understanding of its mechanism and in vivo relevance may lead to a better understanding of basic neurobiological processes such as neurodevelopment and the normal functions of the adult mammalian brain.