Intracellular pattern formation

细胞内模式形成

基本信息

批准号：
10398948
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/10398948
关键词：
Address Alleles Animals Anterior Apical Armadillo Repeat Biochemical CCNE1 gene Calcium-Binding Proteins Calmodulin-Binding Proteins Cell Polarity Cell division Cells 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 type cilium motility kinetosome molecular domain mutant novel polarized cell reverse genetics scaffold 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.

项目摘要/摘要我们将研究细胞骨架细胞器如何组织成细胞中的模式。西里亚母亲的田地在上皮细胞和内部毛细胞中的立体丝菌的行是物理上的例子重要的细胞器图案。已知的途径不满足解释细胞器模式形式。纤毛的生物（纤毛）组装很少的复杂表面（皮质）模式。纤毛忠实地复制其在细胞分裂期间的皮质模式，并在其复杂性中进行皮质模式在人群中几乎保持不变。那即使是微妙的与正常模式的不同（例如可以在许多世代中检测和分析突变或创伤。在遗传模型中纤毛四心苯胺嗜热，包括纤毛在内的数百个皮质细胞器，沿着前后和圆周（左右）轴。我们最近确定了几个因果突变经典四膜模式突变体，其中细胞器在不正确的位置组装。我们发现河马途径激酶和细胞周期蛋白E的直系同源物对于在前后构图上构图至关重要轴。我们确定了HPO1的强候选者，一种调节细胞器位置的蛋白质细胞的圆周轴。这些模式调节蛋白的分子活性 ACT及其受限皮质局部化的基础仍然未知。我们将探索分子驱动四膜模式形成的途径的组成，研究模式调节蛋白质，并开发遗传和生化筛选，以系统地揭示细胞内模式的原理通过公正的方法。目标1的总体目标是发现控制细胞器的初始位置的“早期”河马信号的分子电路在四膜膜的前后细胞轴上的细胞分裂期间的这种形式。 AIM 2将调查如何 “晚期”河马信号通路和细胞周期蛋白E相互作用（以相互拮抗的方式）诱导和保持在分裂平面形成的皮质结构。 AIM 3将调查调节的因素圆周图案，包括HPO1，一种位于细胞右侧的蛋白质。