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

神经元之间通过一种名为突触的结构相互通信，神经元通信对我们的大脑功能至关重要。突触中经验诱发的电活动可以加强(称为长时程增强[LTP])或减弱(称为长时程抑制[LTD])神经元通信。LTP和LTD是突触可塑性的表现，是与学习和记忆相关的细胞。众所周知，一种称为蛋白磷酸酶-1(PP1)的酶需要被抑制剂-1抑制才能发生增强(LTP)，而PP1需要完全激活才能发生弱化(LTD)。此外，夏博士还发现，PP1需要被神经元蛋白“运送”到突触中的正确位置才能发挥作用。Neurabin和Inhibitor-1在LTD和LTP中竞争PP1的确切机制尚不清楚。这个项目将检验这样一种假设，即这些蛋白质的磷酸化状态调节它们相互作用和发挥作用的能力。它描述了控制PP1与抑制物-1和Neurabin结合强度的潜在机制。该项目解决了一个非常重要的主题，即磷酸酶及其相互作用的蛋白可能在调节突触传递和LTD/LTP中发挥作用。夏博士将使用多学科方法--荧光共振能量转移(FRET)成像技术，结合分子生物学/生物化学和细胞电生理学技术--来验证他的假设。资金还将用于培训研究生进行论文研究，以及培训少数族裔高中/本科生进行暑期研究。当地的大学，如泽维尔大学和南方大学，为路易斯安那州立大学提供了许多热衷于生物学基础研究的学生。他们的兴趣将得到培养和促进。这项拟议的研究的成功完成将有助于阐明PP1在神经回路形成以及学习和记忆等高级认知中的潜在分子机制

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