FUNCTION OF G PROTEIN AND PCP2 IN CEREBELLUM DEVELOPMENT

描述（改编自申请人的摘要）：细胞外刺激是 通过信号级联传递到细胞内效应物， 大分子的相互作用。目前的研究建议介绍 本科生调查功能的影响两个 相互作用蛋白：G蛋白亚基Galpha 0，脑富集细胞信号 蛋白质，和浦肯野细胞蛋白2（Pcp 2），一种蛋白质，它只 在小脑和眼睛中表达，并且在退化的 浦肯野细胞。小脑浦肯野细胞对于整合感觉神经元是至关重要的 和运动输入，并且已知在各种神经系统中退化 紊乱虽然Pcp 2的功能尚不清楚，但它与G 蛋白质Galpha 0表明这两种蛋白质可能在细胞信号中起作用 小脑发育过程中的重要通路。关于这一点的工作假设 一项提议的研究是，Galpha 0和Pcp 2的相互作用是细胞的一部分， 正常小脑发育的信号通路。为了验证这个假设， 细胞培养、免疫组织化学、免疫细胞化学和行为研究 将进行双敲除小鼠的研究。两个具体目标是：1） 在细胞和亚细胞水平上共定位Galpha 0和Pcp 2; 2） 分析缺乏Galpha 0和Pcp 2的小鼠的表型。结果 这些实验将提供关于函数关系的信息， 在Galpha 0和Pcp 2之间，这可能在信号传导中很重要。 在神经元发育和疾病的级联，并将有重要的 对理解G蛋白在神经系统中的基本作用的意义 系统

DESCRIPTION (adapted from the applicant's abstract): Extracellular stimuli are transmitted to intracellular effectors by signaling cascades that involve interactions of macromolecules. The present research proposal introduces undergraduate students to investigate the functional implications of two interacting proteins: G protein subunit Galpha0, a brain-enriched cell signal protein, and the Purkinje cell protein 2 (Pcp2), a protein which is only expressed in the cerebellum and the eye, and which is depleted in degenerated Purkinje cells. Cerebellar Purkinje cells are essential for integrating sensory and motor input and are known to degenerate in a variety of neurological disorders. While the function of Pcp2 remains unknown, its interaction with G protein Galpha0 suggests that the two proteins may function in a cell signal pathway important during cerebellar development. The working hypothesis for the proposed research is that interaction of Galpha0 and Pcp2 is part of a cell signaling pathway for normal cerebellum development. To test the hypothesis, cell culture, immunohistochemistry, immunocytochemistry, and behavioral studies of double knock-out mice will be performed. The two specific aims are: 1) to co-localize Galpha0 and Pcp2 at the cellular and subcellular levels; 2) to analyze the phenotypes of mice lacking both Galpha0 and Pcp2. Results from these experiments will provide information on the functional relationship between Galpha0 and Pcp2, which is likely to be important in the signaling cascade during neuronal development and disorders, and will have important implications for understanding the fundamental role of G protein in the nervous system.