Role of MAGUKs in assembly of transmembrane receptor signaling networks

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Dopamine is an important chemical made naturally by the brain. Dopamine communicates with the brain cells by attaching itself to specific proteins called receptors. These receptors are all located outside the cell. In humans, five different types of dopamine receptors exist (D1, D2, D3, D4 and D5). Following the attachment of dopamine, receptors are turn on like a switch that transmits a biochemical signal inside the cell. Recent studies in our laboratory have identified a protein called SAP102 that glues itself to the dopamine D1 receptor. In this proposal we will capitalize on these new findings to explore in a more comprehensive manner how SAP102 glues to the D1 receptor and control dopamine effects. Results obtained from these studies will help us to understand how dopamine and its receptors control brain functions such as learning and memory. In fact, inhibition of SAP102 gene leads to an impaired learning function in mice. Finally, our studies will provide a better insight into how dopamine receptors are regulated and potentially lead to development of new and more efficacious drugs that are specific for the dopamine D1 receptor.