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基因)在不同脑区的广泛分布表明PTEN是重要的，但PTEN在各种脑功能中的确切作用在很大程度上是未知的。培养细胞中的PTEN与膜相关鸟氨酸激酶倒置2(MAGI-2)相互作用，MAGI-2是一种位于突触中的蛋白质，将两个脑细胞连接在一起。MAGI-2还与大脑功能重要的各种分子相互作用。根据各种间接证据和我们的初步结果，我们假设PTEN通过其与MAGI-2的直接蛋白质-蛋白质相互作用(偶联)调节两个脑区(即前额叶皮质和海马体)的功能。我们将使用各种方法和技术在老鼠身上批判性地检验这一假说。这项研究是新颖的，因为它将回答完全未知的问题，即PTEN是否以及如何通过其与MAGI-2的蛋白质-蛋白质相互作用来调节各种大脑功能。这些研究很重要，有两个原因：(1)虽然哺乳动物大脑中的数十亿个神经元通过特殊的连接(突触)相互通信，但这些研究将确定PTEN和MAGI-2在调节突触功能中的重要性；(2)这些研究获得的知识将为更好地了解前额叶和海马区依赖的功能，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.