F-Actin Remodeling at Newly Forming Cell-Cell Junctions

新形成的细胞-细胞连接处的 F-肌动蛋白重塑

基本信息

批准号：
6836413
负责人：
ANNA M SOKAC
金额：
$ 4.89万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2007-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Epithelial cell sheets drive morphogenesis, and in adult tissues intact epithelia provide active barriers between tissue compartments. These functions require cells of the epithelia to be polarized and this polarity depends on the adhesion of cells-to-cells and cells-to-substrate. Loss of cell-cell adhesion precipitates several human disorders including, degenerative skin blistering diseases, cystic kidney diseases and cancer. In fact, diminished cell adhesion directly correlates with invasiveness of malignant cells; and invasiveness of carcinomas is countered by rescuing cell-cell adhesion. Given the necessity of cell-cell adhesion to the normal and pathological physiology of epithelia, knowing how cell-cell junctions are assembled and maintained is biologically and clinically significant. The Aims of this proposed work address the role played by actin in assembly/stability of cell-cell junctions in the primary epithelium of the Drosophila embryo. Specifically, the function of Nullo, a cell-cell junction protein that may coordinate membrane insertion with actin remodeling at junctions, will be studied using high-temporal and -spatial resolution confocal microscopy (3-dimensional and 4-dimensional). The goals of the work are 1) to characterize assembly/maintenance of cell-cell junctions with respect to actin dynamics in this model system, and 2) to demonstrate a cellular mechanism whereby membrane insertion at junctions orchestrates actin remodeling at junctions.

描述（由申请人提供）：上皮细胞表驱动形态发生，在成年组织中，完整的上皮在组织室之间提供了活跃的屏障。这些功能需要上皮细胞的细胞两极化，并且这种极性取决于细胞对细胞和细胞至底物的粘附。细胞细胞粘附的丧失会导致几种人类疾病，包括退化性皮肤泡沫，囊性肾脏疾病和癌症。实际上，细胞粘附减少直接与恶性细胞的侵入性相关。通过挽救细胞 - 细胞粘附来抵消癌的侵入性。鉴于细胞细胞粘附对上皮的正常和病理生理的必要性，因此知道细胞 - 细胞连接的组装和维护是生物学和临床上的显着意义。这项提出的工作的目的探讨了肌动蛋白在果蝇胚胎主要上皮中细胞连接处的组装/稳定性中所起的作用。具体而言，将使用高频和 - 空间分辨率共聚焦显微镜（3维和4维）研究Nullo（一种可能与肌动蛋白重塑插入膜插入的细胞 - 细胞连接蛋白的功能。工作的目标是1）表征该模型系统中肌动蛋白动力学的细胞细胞连接的组装/维护，以及2）证明一个细胞机制，从而在连接处的膜插入在连接处协调肌动蛋白的重塑。