Fat-Dachsous signaling in growth control and planar cell polarity

生长控制和平面细胞极性中的脂肪-达克索信号传导

基本信息

批准号：
8828794
负责人：
SETH S BLAIR
金额：
$ 31.89万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-08-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8828794
关键词：
Beryllium Binding Binding Sites Biological Assay Biology Cell Death Cell surface Cells Data Dimerization Distal Drosophila genus Enhancers Extracellular Domain Failure Family Fatty acid glycerol esters Genes Genetic Transcription Golgi Apparatus Grant Growth Health Human Human Development In Vitro Indium Integral Membrane Protein Joints Knowledge Light Link Malignant Neoplasms Maps Mediating MicroRNAs Molecular Genetics Mutation Myosin ATPase Organism Pathology Pathway interactions Pattern Phenotype Phosphotransferases Play Protein Binding Protein Binding Domain Protein Kinase Proteins RNA Interference Regulation Resources Response Elements Role Scallop Series Signal Transduction Speed Structure Testing appendage cofactor design extracellular gain of function in vitro Assay in vitro activity loss of function member mutant organ growth overexpression planar cell polarity polarized cell receptor research study screening tool transcription factor tumorigenesis tumorigenic

项目摘要

DESCRIPTION (provided by applicant): This proposal outlines a series of experiments designed to test the regulation of an important intracellular pathway for controlling growth, cell death and patterning in developing organisms: that mediated by the Hippo and Warts protein kinases. This pathway plays a major role in controlling organ growth, and misregulation of the pathway is tumorigenic, but little is known about how it is controlled. We are concentrating on how this pathway is regulated by the large Drosophila protocadherins Fat and Dachsous. The extracellular domains of these two transmembrane proteins bind each other, and this suppresses growth by activating the Hippo pathway. However, the mechanisms connecting Fat and Dachsous to the Hippo pathway are poorly understood. First, we are dissecting the activities of the intracellular domains of Fat, and are using that to develop an in vitro RNAi screen for molecules required for Fat activity. Second, we are examining how boundaries and gradients of Fat and Dachsous expression, and the resultant polarization of Fat and Dachsous on cell surfaces, inhibits the Hippo pathway and triggers growth. Third, we are examining the role of a downstream negative regulator of Fat activity, the atypical myosin Dachs/Myosin29D, and its regulator Approximated. Finally, we are examining how the Hippo pathway combines with additional (especially spatial) information to regulate the expression of an important downstream target, the miRNA bantam.

描述（由申请人提供）：该提案概述了一系列实验，旨在测试对发展中生物体的生长，细胞死亡和模式的重要细胞内途径的调节：由河马和疣蛋白激酶介导的。该途径在控制器官的生长中起着主要作用，途径的正调是肿瘤性的，但对其控制方式鲜为人知。我们专注于该途径如何受到大型果蝇原粘蛋白脂肪和陶氏的调节。这两个跨膜蛋白的细胞外域相互结合，这通过激活河马途径来抑制生长。但是，将脂肪和二豆与河马途径相连的机制知之甚少。首先，我们正在解剖脂肪的细胞内结构域的活性，并使用它来开发体外RNAi筛选脂肪活性所需的分子。其次，我们正在研究脂肪和二豆表达的边界和梯度，以及脂肪和二豆在细胞表面上的极化，抑制河马途径并触发生长。第三，我们正在研究脂肪活性下游负调节剂，非典型肌球蛋白dACHS/肌动蛋白29D及其调节剂的作用。最后，我们正在研究河马途径如何与其他（尤其是空间）信息结合起来，以调节重要的下游目标miRNA矮脚鸡的表达。