Signaling Pathways and Microtubule Function

信号通路和微管功能

• 批准号: 6504761
• 负责人: DAN ESHEL
• 金额: $ 14.67万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6504761
• 关键词: biological signal transduction; cell cycle; fungal genetics; gene expression; gene mutation; guanosinetriphosphatases; microtubules; mitogen activated protein kinase; molecular cloning; protein structure function; yeasts

DESCRIPTION (provided by applicant): Our long-term goal is to understand how signaling pathways in the cell control properties of microtubules. Specifically, we will concentrate on possible roles of the protein kinase C (PKC)-mediated mitogen activated protein kinase (MAPK) and the Cdc42pICdc24p pathways in controlling microtubule stability. Our working hypothesis is based on preliminary studies in which we identified two genes involved in these pathways as multicopy suppressors of mutations in the anaphase motor proteins Cin8 and Dyn1. The genes are KRE6 that was reported to suppress the lysis phenotype of pkc1, the yeast PKC homolog, and GIC1, an effector of Cdc42p. In other preliminary experiments, we found that these suppressors may act by stabilizing microtubules. Our specific aims will be (1) to identify additional suppressors related to these pathways, (2) to characterize the effect of the suppressors on microtubule function, and (3) to study the relation between microtubule function and the above pathways. For aim 1 we will continue to investigate suppressor clones that we previously isolated. In aim 2 we will study organization and function of cytoplasmic and nuclear microtubules under the effect of the suppressors. In aim 3 we will use a genetic approach to investigate the effect of mutations in, and overexpression of, genes related to the above pathways on microtubule properties. Results obtained in this project will provide new and important information in two contexts. First, they will show how conserved signaling mechanisms that regulate polarized growth and a variety of cortical events affect microtubule--dependent processes. Second, they will show how these pathways interact.

描述（由申请人提供）：我们的长期目标是了解细胞中的信号通路如何控制微管的特性。具体来说，我们将重点关注蛋白激酶 C (PKC) 介导的丝裂原激活蛋白激酶 (MAPK) 和 Cdc42pICdc24p 通路在控制微管稳定性中的可能作用。我们的工作假设基于初步研究，其中我们确定了参与这些途径的两个基因作为后期运动蛋白 Cin8 和 Dyn1 突变的多拷贝抑制因子。这些基因是 KRE6，据报道可以抑制 pkc1（酵母 PKC 同源物）和 GIC1（Cdc42p 的效应子）的裂解表型。在其他初步实验中，我们发现这些抑制剂可能通过稳定微管发挥作用。我们的具体目标是（1）识别与这些途径相关的其他抑制因子，（2）表征抑制因子对微管功能的影响，以及（3）研究微管功能与上述途径之间的关系。对于目标 1，我们将继续研究我们之前分离的抑制克隆。在目标 2 中，我们将研究抑制因子作用下细胞质和核微管的组织和功能。在目标 3 中，我们将使用遗传学方法来研究与上述途径相关的基因突变和过度表达对微管特性的影响。该项目获得的结果将在两个方面提供新的重要信息。首先，他们将展示调节极化生长和各种皮质事件的保守信号机制如何影响微管依赖性过程。其次，他们将展示这些途径如何相互作用。