MAP1A AND MAP1B--SYNTHESIS, STRUCTURE/FUNCTION

描述（研究者摘要）：微管和 微管相关蛋白（MAPs）是丝状超微结构 轴突和树突形成所必需的成分。 一个功能 微管的作用是在细胞之间运输轴突“建筑材料”， 索马和轴突。 微管相关蛋白1A和1B，MAP1 蛋白质，是结构上相关的蛋白质，具有与 微管、微丝和常见的多肽亚基。 MAP 1 蛋白质是轴突中最丰富的微管相关蛋白，然而 其功能仍然未知。 广泛推测MAP1蛋白质 与微管相互作用以建立、组织和维持 轴突细胞骨架的结构。 我们的主要目标是测试这个 通过确定改变MAP1的超微结构后果， 浓度和通过操纵特定的分子内和分子间 MAP 1蛋白的相互作用。 对MAP1分子的深入了解 相互作用将为操纵MAP1活动提供基础， 优化神经系统再生，并识别和防止任何 由MAP1活性改变引起的特定疾病。 本研究的目的有五个：1）研究MAP1蛋白酶的活性 这极大地改变了MAP1蛋白质的结构。 MAP1蛋白酶 识别序列将被识别。 分子内相互作用 将定义MAP 1多蛋白水解所需的条件。 这些信息 将在未来的研究中用于开发MAP 1蛋白酶抑制剂， 确定蛋白酶抑制对神经元功能的影响， 纯化MAP 1蛋白酶。 2)为了鉴定MAP1亚基相互作用， 对微管结合活性至关重要。 需要这些信息， 建立一种机制，通过这种机制，MAP1蛋白组织和加强 轴突细胞骨架 3)为了确定一级氨基酸序列， 70 kDa的蛋白质与MAP1蛋白。 这种分子是一种 MAP1蛋白酶的候选者。 4)来衡量 增加MAP1B对微管结构和神经元功能的影响 来延伸轴突。 5)测量删除MAP 1B对 在转基因小鼠中的神经元细胞骨架的组织。 最后一 两个目标直接测试MAP1蛋白在建立、组织、 和维持轴突细胞骨架。

DESCRIPTION (Investigator's Abstract): Microtubules and microtubule-associated proteins (MAPs) are filamentous ultrastructural components that are essential for axon and dendrite formation. One function of microtubules is to transport axon "building materials" between the cell soma and the axon. Microtubules associated proteins 1A and 1B, the MAP1 proteins, are structurally related proteins with binding sites for microtubules, microfilaments, and common polypeptide subunits. The MAP 1 proteins are the most abundant microtubule-associated proteins in axons, yet their function remains unknown. MAP1 proteins are widely speculated to interact with microtubules to establish, organize, and maintain the structure of the axonal cytoskeleton. Our broad objective is to test this hypothesis by determining the ultrastructural consequences of changing MAP1 concentration and by manipulating specific intra- and intermolecular interactions of MAP 1 protein. A thorough understanding of MAP1 molecular interactions will provide the foundation for manipulating MAP1 activity to optimize nervous system regeneration and to identify and prevent any specific diseases caused by altered MAP1 activity. This project has five aims: 1) To characterize a MAP1 protease activity that dramatically alters the structure of MAP1 proteins. The MAP1 protease recognition sequence will be identified. The intramolecular interactions required for MAP1 polyprotein proteolysis will be defined. This information will be used in future studies to develop MAP1 protease inhibitors, to determine the consequences of protease inhibition on neuron function, and to purify the MAP1 protease. 2) To identify MAP1 subunit interactions that are essential for microtubule binding activity. This information is needed to establish a mechanism by which MAP1 proteins organize and strengthen the axonal cytoskeleton. 3) to determine the primary amino acid sequence of a 70 kDa protein associated with the MAP1 proteins. This molecule is a candidate for the MAP1 protease. 4) to measure the effects of decreasing and increasing MAP1B on microtubule organization and the ability of neurons to extend axons. 5) To measure the effect of deleting MAP1B on the organization of the neuronal cytoskeleton in a transgenic mouse. The last two aims directly test the role of MAP1 proteins in establishing, organizing and maintaining the axonal cytoskeleton.