Regulation of brain function by PTEN

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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.