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

Neurabin 和抑制剂 1 在 LTD 和 LTP 表达中竞争 PP1 结合

• 批准号: 0824393
• 负责人: Houhui Xia
• 金额: $ 38.39万
• 依托单位: Louisiana State University Health Sciences Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0824393&HistoricalAwards=false
• 关键词: Neurabin; inhibitor; Compete; PP1; Binding

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

神经元通过一种叫做突触的结构相互交流，神经元的交流对我们的大脑功能至关重要。 神经元通讯可以被加强（称为长时程增强[LTP]）或减弱（称为长时程抑制[LTD]），以响应经验诱导的突触电活动。 LTP和LTD是突触可塑性的表现，与学习和记忆相关的细胞。 已知一种称为蛋白磷酸酶-1（PP 1）的酶需要被抑制剂-1抑制以发生强化（LTP），而PP 1需要被完全激活以发生弱化（LTD）。 此外，夏博士还发现，PP 1需要通过神经肽蛋白“递送”到突触中的正确位置才能发挥作用。 在LTD和LTP中，neurabin和inhibitor-1竞争PP 1的确切机制尚不清楚。 该项目将测试这些蛋白质的磷酸化状态调节它们相互作用和功能的能力的假设。 它表征了控制PP 1与抑制剂-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，以及培训少数民族高中/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情的学生谁想要从事生物学基础研究。 他们的兴趣将得到培养和促进。 成功完成拟议的研究将揭示PP 1在神经回路形成以及更高水平的认知（如学习和记忆）中功能的潜在分子机制。