Intracellular pattern formation

细胞内模式形成

基本信息

批准号：
10594485
负责人：
JACEK GAERTIG
金额：
$ 30.2万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10594485
关键词：
Alleles Animals Anterior Apical Armadillo Repeat Biochemical CCNE1 gene Calcium-Binding Proteins Calmodulin-Binding Proteins Cell Polarity Cell division Cells Centrosome Cilia Complex Cues Cytoskeleton Daughter Epithelial Cells Generations Genes Genetic Genetic Models Genetic Screening Goals Image Inner Hair Cells Interphase Joubert syndrome Labyrinth Left Link Maintenance Malaria Maps Modeling Molecular Morphogenesis Mutation Natural regeneration Oral Organelles Orthologous Gene Outcome Parasites Pathway interactions Pattern Pattern Formation Phenocopy Phenotype Phosphotransferases Physiological Plasmodium Population Positioning Attribute Property Proteins Resolution Role Sensory Side Signal Transduction Structure Surface Tertiary Protein Structure Testing Tetrahymena Tetrahymena thermophila Trauma Work airway epithelium analog antagonist causal variant cell assembly cell type cilium motility kinetosome molecular domain mutant novel polarized cell reverse genetics scaffold synergism tool

项目摘要

PROJECT SUMMARY/ABSTRACT We will investigate how cytoskeletal organelles organize into patterns in the cell. The fields of motile cilia in epithelial cells and the rows of stereocilia in the inner hair cells are examples of physiologically- important organelle patterns. The known pathways do not satisfactorily explain how organelle patterns form. The ciliated protists (ciliates) assemble unusually complex surface (cortical) patterns. Ciliates faithfully duplicate their cortical pattern during cell division and, despite its complexity, the cortical pattern remains nearly invariable in a population. Thus, even subtle deviations from the normal pattern (e.g. due to a mutation or trauma) can be detected and analyzed over many generations. In the genetic model ciliate Tetrahymena thermophila, hundreds of cortical organelles, including cilia, are arranged along the anteroposterior and circumferential (left-right) axes. We recently identified causal mutations in several classical Tetrahymena pattern mutants, in which organelles assemble at incorrect positions. We found that orthologs of the Hippo pathway kinases and cyclin E are critical for patterning on the anteroposterior axis. We identified a strong candidate for Hpo1, a protein that regulates the positions of organelles on the cell’s circumferential axis. The molecular activities through which these pattern-regulating proteins act, and the basis of their restricted cortical localizations, remain unknown. We will explore the molecular composition of the pathways that drive pattern formation in Tetrahymena, study the properties of the pattern-regulating proteins and develop genetic and biochemical screens to systematically unravel the principles of intracellular patterning through unbiased approaches. The overarching goal for Aim 1 is to uncover the molecular circuitry of “early” Hippo signaling that controls the initial positions of organelles that form during cell division on the anteroposterior cell axis in Tetrahymena. Aim 2 will investigate how the “late” Hippo signaling circuit and cyclin E interact (in a mutually antagonistic manner) to induce and maintain cortical structures that form at the division plane. Aim 3 will investigate factors that regulate the circumferential pattern, including Hpo1, a protein that localizes to the right side of the cell.

项目概要/摘要我们将研究细胞骨架细胞器如何在细胞中组织成运动纤毛区域。上皮细胞中的静纤毛和内毛细胞中的静纤毛行是生理学的例子重要的细胞器模式。已知的途径不能令人满意地解释细胞器模式。纤毛原生生物（纤毛虫）组装异常复杂的表面（皮质）图案。忠实地复制细胞分裂过程中的皮质模式，尽管其复杂性，皮质模式因此，即使与正常模式有细微的偏差（例如由于突变或创伤）可以在遗传模型中检测和分析很多代。纤毛虫嗜热四膜虫，数百个皮质细胞器，包括纤毛，沿着我们最近在几个轴上发现了因果突变。我们发现了经典的四膜虫模式突变体，其中细胞器组装在错误的位置。 Hippo 通路激酶和细胞周期蛋白 E 的直向同源物对于前后位图的模式化至关重要我们发现了 Hpo1 的有力候选者，这是一种调节细胞器位置的蛋白质。这些模式调节蛋白通过细胞的圆周轴进行分子活动。行为及其受限皮质定位的基础仍然未知，我们将探索分子机制。驱动四膜虫模式形成的途径的组成，研究模式调节蛋白并开发遗传和生化筛选以系统地揭示通过公正的方法进行细胞内模式化的原则目标 1 的总体目标是揭示控制细胞器初始位置的“早期”河马信号传导的分子电路 Aim 2 将研究四膜虫前后细胞轴上的细胞分裂过程中形成的细胞。 “晚期”Hippo 信号通路和细胞周期蛋白 E 相互作用（以相互拮抗的方式）以诱导和维持分裂平面上形成的皮质结构。目标 3 将研究调节分裂平面的因素。圆周模式，包括 Hpo1，一种定位于细胞右侧的蛋白质。