DEVELOPMENT OF CELL POLARITY IN BUDDING YEAST

描述(逐字摘自申请人的摘要)：酿酒酵母是一种 由于其强大的功能而成为研究细胞极性发育的优秀生物 遗传学，它的简单性，观察极性发展的能力 在一个细胞群体中同步存在，并且存在大量突变和 细胞极性的分子标记。研究将确定CDC42 GTP酶如何 控制肌动蛋白的组织，以及肌动蛋白如何介导极化内吞作用。 37个定点定向的cdc42突变体将在 通透性酵母与肌动蛋白组装活性酵母提取物的关系 生物化学活性以体内功能，并用于遗传筛选以 确定下游路径的组件。Cdc42效应器包的角色 形态发生中的激酶将通过遗传学和化学遗传学来阐明 战略。在假菌丝生长中有缺陷的特殊的CDC42等位基因将是 为更深入地了解真菌的分子基础而进行的研究 二形性，许多真菌病原体的特征。最后，一个复杂的 一组相互作用的蛋白质将内细胞膜连接到Arp2/3复合体， 以及这些蛋白是如何由在这一研究中发现的新的方舟激酶调节的 实验室，将进行调查。

DESCRIPTION (Verbatim from the applicant's abstract): S. cerevisiae is an excellent organism for studies of cell polarity development due to its powerful genetics, its simplicity, the ability to observe polarity development synchronously in a cell population, and existence of numerous mutations and molecular markers for cell polarity. Studies will determine how Cdc42 GTPase controls actin organization, and how actin mediates polarized endocytosis. Thirty-seven site-directed cdc42 mutants will be characterized biochemically in permeabilized yeast and in actin-assembly competent yeast extracts to relate biochemical activities to in vivo functions, and used in genetic screens to identify components of downstream pathways. Roles for Cdc42 effector Pak kinases in morphogenesis will be elucidated by genetic and chemical-genetic strategies. Special cdc42 alleles defective in pseudohyphal growth will be studied to provide a deeper understanding of the molecular basis for fungal dimorphism, a characteristic of many fungal pathogens. Finally, how a complex set of interacting proteins links endocytic membranes to the Arp2/3 complex, and how these proteins are regulated by novel Ark kinases discovered in this laboratory, will be investigated.