Regulation of brain function by PTEN

PTEN酶（10号染色体上缺失的磷酸酶和紧张素同源物）在大脑各个区域的广泛分布表明PTEN很重要，但PTEN在各种大脑功能中所起的确切作用在很大程度上是未知的。培养细胞中的PTEN与膜相关鸟苷激酶2 （MAGI-2）相互作用，MAGI-2是一种位于连接两个脑细胞的突触中的蛋白质。MAGI-2还与各种对大脑功能重要的分子相互作用。根据各种间接证据和我们的初步结果，我们假设PTEN通过与MAGI-2的直接蛋白-蛋白相互作用（偶联）调节两个大脑区域（即前额叶皮层和海马）的功能。我们将采用各种方法和技术在大鼠中严格验证这一假设。这项研究是新颖的，因为它将回答PTEN是否以及如何通过与MAGI-2的蛋白质-蛋白质相互作用调节各种大脑功能的完全未知的问题。这些研究有两个重要的原因：(1)哺乳动物大脑中数十亿的神经元通过专门的连接（突触）相互交流，这些研究将确定PTEN和MAGI-2在调节突触功能中的重要性；(2)从这些研究中获得的知识将为更好地理解前额叶和海马体依赖的功能（如学习和记忆）提供数据。

The widespread distribution of the enzyme PTEN (phosphatase and tensin homolog deleted on chromosome 10) in various brain regions suggests PTEN is important, but the exact roles PTEN plays in various brain functions are largely unknown. PTEN in cultured cells interacts with the membrane-associated guanylate-kinase inverted 2 (MAGI-2), a protein located in the synapses that connect two brain cells together. MAGI-2 also interacts with various molecules important for brain function. According to various lines of indirect evidence and our preliminary results, we hypothesize that PTEN regulates the function of two brain areas (i.e., the prefrontal cortex and hippocampus) through its direct protein-protein interaction (coupling) with MAGI-2. We will employ various methods and techniques to critically test this hypothesis in rats. This research is novel as it will answer the entirely unknown questions of whether and how PTEN regulates various brain functions via its protein-protein interaction with MAGI-2. These studies are important for two reasons: (1) while billions of neurons in the mammalian brain communicate with each other via specialized junctions (synapses), these studies will determine the importance of PTEN and MAGI-2 in regulating synaptic function; and (2) knowledge gained from these studies will provide data for a better understanding of prefrontal- and hippocampus-dependent functions, such as learning and memory.