Role of MAGUKs in assembly of transmembrane receptor signaling networks

多巴胺是大脑自然产生的一种重要化学物质。多巴胺通过附着在一种叫做受体的特殊蛋白质上与脑细胞进行交流。这些受体都位于细胞外。在人类中，存在五种不同类型的多巴胺受体（D1，D2，D3，D4和D5）。多巴胺附着后，受体就像一个开关一样被打开，在细胞内传递生化信号。我们实验室最近的研究已经确定了一种名为SAP 102的蛋白质，它可以将自己粘附到多巴胺D1受体上。在本提案中，我们将利用这些新发现，以更全面的方式探索SAP 102如何与D1受体结合并控制多巴胺效应。从这些研究中获得的结果将有助于我们了解多巴胺及其受体如何控制大脑功能，如学习和记忆。事实上，抑制SAP102基因导致小鼠学习功能受损。最后，我们的研究将更好地了解多巴胺受体是如何调节的，并可能导致开发新的和更有效的药物，这些药物对多巴胺D1受体具有特异性。

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.