Neurabin and inhibitor-1 Compete for PP1 Binding in LTD and LTP Expression

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Neurons communicate with each other through a structure called the synapse, and neuronal communication is critical for our brain function. Neuronal communication can be strengthened (called long term potentiation [LTP]) or weakened (called long term depression [LTD]) in response to experience-induced electrical activity in synapses. LTP and LTD are manifestations of synaptic plasticity, the cellular correlate for learning and memory. It is known that an enzyme called protein phosphatase-1 (PP1) needs to be inhibited by inhibitor-1 for the strengthening (LTP) to occur, while PP1 needs to be fully activated for the weakening (LTD) to occur. Moreover, Dr. Xia has discovered that PP1 needs to be "delivered" to the right place in the synapse by the protein neurabin for its action. The exact mechanism underlying the competition for PP1 by neurabin and inhibitor-1 in LTD and LTP is not known. This project will test the hypothesis that the phosphorylation state of these proteins modulates their ability to interact with each other and function. It characterizes the underlying mechanism controlling the strength of PP1 binding to inhibitor-1 and neurabin. The project addresses a very important topic, that phosphatases and their interacting proteins may have a role in modulating synaptic transmission and LTD/LTP. Dr. Xia will use multidisciplinary approaches - fluorescence resonance energy transfer (FRET) imaging technique, in combination with molecular biology/biochemistry and cellular electrophysiology techniques - to test his hypotheses. Funding will also be used to train graduate students on dissertation research as well as to train minority high-school/undergraduate students in summer research. Local universities, such as Xavier University and Southern University, have provided LSU with many enthusiastic students who want to pursue basic research in biology. Their interest will be nurtured and promoted. Successful completion of the proposed study will shed light on the underlying molecular mechanism of PP1 function in neural circuitry formation as well as higher level cognition, such as learning and memory