Genetic Control of Tubulin Function in Development

发育过程中微管蛋白功能的遗传控制

基本信息

批准号：
6917126
负责人：
ELIZABETH C. RAFF
金额：
$ 33.28万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-09-01 至 2007-06-30
项目状态：
已结题

项目摘要

DESCRIPTION:A fundamental question in biology is how functional three-dimensional cell structure is formed. The proposed research addresses this question by genetic and molecular studies of microtubule function in Drosophila melanogaster. Microtubules are ubiquitous eukaryotic organelles required for many cellular processes, including cell shape, cell division, and the motility of cilia and flagella. The basic subunit of microtubules is the alpha, Beta-tubulin heterodimer. Multicellular eukaryotes express multiple tubulin isoforms encoded in multi-gene families; additional tubulin diversity is generated by post-translational modifications. Each microtubule structure is unique in supramolecular architecture, mode of function, and total spectrum of constituent proteins. Assembly of different microtubule-based structures thus depends on interactions between tubulin heterodimers, and between tubulins and other proteins. The proposed research focuses on the role of tubulin diversity in determining the specificity of microtubule assembly and function. Because microtubule arrays are similar in all organisms, the results obtained in Drosophila are directly relevant to understanding microtubule function in other species, including vertebrates. The first goal of the proposed research is to determine the role of tubulin primary structure in specifying the architecture of different classes of microtubules. These studies use as a model system analysis of the multiple microtubule processes in spermatogenesis mediated by the testis-specific beta2-tubulin isoform. The primary focus is assembly of the motile axoneme, a deeply conserved organelle present in animals, plants, and protists. A major objective is to determine the molecular mechanisms by which distinct tubulin-associated components of the sperm flagella axoneme are specified. The second goal of the proposed work is to determine the role of differential expression of different tubulin isoforms in development and cell differentiation. These studies focus on analysis of the function of the essential, structurally divergent beta3-tubulin isoform in neuronal patterning in the developing adult visual system and in the larval mechanosensory organs. Transient beta3 expression during differentiation has permanent consequences for cell function, even when beta3 is no longer present. The primary aim is to determine how transient expression of beta3-tubulin during development modulates the microtubule cytoskeleton in the differentiated cell.

描述：生物学的基本问题是功能形成了三维细胞结构。拟议的研究讲话通过微管功能的遗传和分子研究这个问题果蝇Melanogaster。微管是无处不在的真核细胞器许多细胞过程所需的，包括细胞形状，细胞分裂和纤毛和鞭毛的运动。微管的基本亚基是alpha， β-微管蛋白异二聚体。多细胞真核生物表达多个小管蛋白在多基因家族中编码的同工型；其他微管蛋白多样性是由翻译后修改产生。每个微管结构都是在超分子体系结构，功能模式和总频谱中唯一组成蛋白。组装不同的基于微管的结构取决于微管蛋白异二聚体之间的相互作用，小管蛋白和其他蛋白质。拟议的研究重点是微管蛋白多样性的作用在确定微管组装和功能的特异性时。因为在所有生物中，微管阵列都是相似的果蝇与理解其他微管功能直接相关物种，包括脊椎动物。拟议研究的第一个目标是确定微管蛋白的作用指定不同类别的体系结构的主要结构微管。这些研究用作多重的模型系统分析由睾丸特异性介导的精子发生中的微管过程 β2-微管蛋白同工型。主要重点是轴突的组装，A 在动物，植物和生物学家中存在深处保守的细胞器。专业目的是确定分子机制，通过指定了精子鞭毛轴突的微管蛋白相关成分。这拟议工作的第二个目标是确定差异的作用发育和细胞中不同小管蛋白同工型的表达分化。这些研究重点是分析在神经元模式中，必需的，结构上不同的β3-微管蛋白同工型在发展中的成年视觉系统和幼虫机械器官中。分化过程中的瞬态beta3表达具有永久后果对于细胞功能，即使不再存在beta3。主要目的是确定发育过程中β3微管蛋白的瞬时表达调节分化细胞中的微管细胞骨架。