Analyses of the role of RHO3 and of the WASP-homologue WAL1 for the maintenance of polarized hyphal growth in Candida albicans

分析 RHO3 和 WASP 同源物 WAL1 在维持白色念珠菌极化菌丝生长中的作用

• 批准号: 5409991
• 负责人: Professor Dr. Jürgen Wendland
• 金额: --
• 依托单位: Institut Mikrobiologie und Biochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5409991?language=en
• 关键词: Analyses; role; RHO3; WASP; homologue

GTP-binding proteins of the Rho-family determine the organization of the actin cytoskeleton and thus morphogenesis and cell shape of eukaryotic cells. Polarized hyphal growth is regarded as a virulence factor of the human fungal pathogen Candida albicans. We could show that the C. albicans homologue of Wiskott-Aldrich Syndrome Proteins (WASP) is required for this process. The mechanism of CaWal1p activation is at present not understood particularly because fungal WASPs lack a G-protein binding domain in contrast to human WASP. Our previous work supports a connection between RHO3 and WAL1 for the organization of the actin cytoskeleton and the maintenance of polarized hyphal growth. In the proposed project a detailed characterization of CaRHO3 is carried out. Deletion mutants will be characterized and the transcriptional regulation of RHO3 during the dimorphic switch will be investigated. Via in vivo time lapse fluorescence microscopy spatial and temporal distribution of Rho3-GFP is determined. Two-hybrid analyses are applied to find additional components of a network that includes Rho3p and Wal1p. This allows to establish a mechanistic connection beween these two proteins and provides insights into the regulation of the cortical actin cytoskeleton and polarized hyphal growth in C. albicans.

Rho家族的GTP结合蛋白决定了肌动蛋白细胞骨架的组织，从而决定了真核细胞的形态发生和细胞形状。极性菌丝生长被认为是人类真菌病原体白色念珠菌的毒力因子。我们可以证明C.该过程需要Wiskott-Aldrich综合征蛋白（WASP）的白色念珠菌同源物。CaWal 1 p激活的机制目前还不清楚，特别是因为真菌WASP与人类WASP相比缺乏G蛋白结合结构域。我们以前的工作支持RHO 3和WAL 1之间的连接，用于肌动蛋白细胞骨架的组织和极化菌丝生长的维持。在所提出的项目中，对CaRH 0 3进行了详细的表征。缺失突变体的特点和转录调控的RH 0 3在二态转换将进行调查。通过体内时间推移荧光显微术确定Rho 3-GFP的空间和时间分布。应用双混合分析来寻找包括Rho 3 p和Wal 1 p的网络的其他组件。这使得这两种蛋白质之间建立了一种机制上的联系，并为C.白色念珠菌