MAP1A AND MAP1B--SYNTHESIS, STRUCTURE/FUNCTION

描述(研究人员摘要)：微管和 微管相关蛋白(MAP)是丝状超微结构 轴突和树突形成所必需的成分。一种功能 微管的作用是在细胞之间运输轴突“建筑材料”。 胞体和轴突。微管相关蛋白1A和1B，MAP1 蛋白质，是结构上相关的蛋白质，具有结合位点 微管、微丝和常见的多肽亚基。地图1 蛋白质是轴突中含量最丰富的微管相关蛋白 它们的功能仍不清楚。MAP1蛋白被广泛推测为 与微管相互作用以建立、组织和维持 轴突细胞骨架的结构。我们的总体目标是测试这一点 通过确定改变MAP1的超微结构后果的假说 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。深入了解MAP1分子 相互作用将为操纵MAP1活动提供基础 优化神经系统再生，识别和预防任何 由MAP1活性改变引起的特定疾病。 该项目有五个目标：1)鉴定MAP1蛋白的活性 这极大地改变了MAP1蛋白的结构。MAP1蛋白水解酶 识别序列将被识别。分子内相互作用 将定义MAP1多蛋白蛋白分解所需的。此信息 将在未来的研究中用于开发MAP1蛋白酶抑制剂，以 确定蛋白水解酶抑制对神经元功能的影响，并 纯化MAP1蛋白酶。2)确定MAP1亚基相互作用 对微管结合活性至关重要。需要此信息才能 建立一种MAP1蛋白组织和加强 轴突细胞骨架。3)测定一种主要氨基酸的序列。 与MAP1蛋白相关的70 kDa蛋白。这种分子是一种 MAP1蛋白水解酶的候选。4)衡量减产的效果 增加MAP1B对微管组织和神经元能力的影响 来延长轴突。5)测量MAP1B缺失对细胞周期的影响 转基因小鼠神经元细胞骨架的组织。最后 两个目的直接测试MAP1蛋白在建立、组织 并维持轴突细胞骨架。

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.