Characterization of Components Interacting with the Cdc42p GTPase

9405972约翰逊这个项目的具体目标是破译控制酿酒酵母细胞极性过程的分子机制。在酵母细胞周期中，响应不同信号的极化生长可以导致几种不同的形态结构的产生，如芽、交配突起和假菌丝。酵母细胞极性装置的三个蛋白质组分：Ras相关的GTP酶CDc42p，通过核苷酸交换激活CDc42p功能的CDc24p和调节CDc42p亚细胞定位的香叶基香叶转移酶的β亚基CDc43p。这些成分在其他真核生物中具有保守的对应物，这表明可能存在共同的机制。该项目将使用遗传和生化技术来识别新的或先前存在的与Cdc42p相互作用的蛋白质，以控制其作为CDc42p的鸟嘌呤核苷酸交换因子的功能，或其定位和与肌动蛋白细胞骨架的相互作用。这个项目的长期目标是了解真核细胞周期中控制细胞形态发生的机制。细胞形态发生是细胞复杂的三维组织发育和维持的过程，对许多细胞和发育过程的控制至关重要，如细胞极性和细胞形状的产生、细胞器在细胞内的运动以及新的细胞表面成分的极化分泌和沉积。基于微管和肌动蛋白的细胞骨架网络在细胞形态发生中起着关键作用。在酿酒酵母中，微管是染色体正确分离和核迁移所必需的，而肌动蛋白微丝是极化生长模式所必需的。酵母中的极化生长同时响应于内部和外部信号，导致不同的形态结构。该提案的目标之一是了解控制这些极化增长模式变化的分子机制。此外，还将确定细胞极性的生长如何与其他细胞过程整合，如细胞周期控制。***

9405972 Johnson The specific goal of this project is to decipher the molecular mechanisms that control the cell polarity process in the yeast Saccharomyces cerevisiae. Polarized growth in response to different signals during the yeast cell cycle can result in the generation of several different morphological structures, such as buds, mating projections and pseudohyphae. Three protein components of the cell polarity apparatus in yeast were previously characterized; the Ras -related GTPase Cdc42p, Cdc24p, which activates Cdc42p function by nucleotide exchange, and Cdc43p, the beta subunit of the geranylgeranyltransferase that regulates Cdc42p subcellular localization. These components have conserved counterparts in other eukaryots, suggesting that common mechanisms may exist. This project will use genetic and biochemical techniques to identify new or pre-existing proteins that interact with Cdc42p to control either its function as a guanine-nucleotide exchange factor for Cdc42p or its localization and interactions with the actin cytoskeleton. %%% The long term objective of this project is to understand the mechanism that control cellular morphogenesis during the eukaryotic cell cycle. Cellular morphogenesis, the process by which the complex, three dimensional organization of the cell is developed and maintained, is crucial for the control of many cellular and developmental processes such as the generation of cell polarity and cell shape, the intracellular movements of organelles, and the polarized secretion and deposition of new cell surface constituents. Microtubules and actin based cytoskeletal networks play a critical role in cellular morphogenesis. In the yeast Saccharomyces cerevisiae, microtubules are required for proper chromosome segregation and nuclear migration while actin microfilaments are necessary for polarized growth patterns. Polarized growth in yeast occurs in response to both internal and external signals, resulting in different m orphological structures. One of the goals of the proposal is to understand the molecular machinery that controls these changes in polarized growth patterns. In addition, it will also be determined how the growth of cell polarity is integrated with other cellular processes, such as cell cycle control. ***