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：
7117319
负责人：
ANNA M SOKAC
金额：
$ 2.7万
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 2007-02-28
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）：上皮细胞片驱动形态发生，并且在成体组织中完整的上皮在组织区室之间提供活性屏障。这些功能需要上皮细胞极化，这种极性取决于细胞与细胞以及细胞与基质的粘附。细胞间粘附力的丧失会导致多种人类疾病，包括退行性皮肤起泡疾病、囊性肾病和癌症。事实上，细胞粘附力的减弱与恶性细胞的侵袭性直接相关。通过挽救细胞间粘附来对抗癌症的侵袭性。鉴于细胞间粘附对上皮正常和病理生理学的必要性，了解细胞间连接如何组装和维持具有生物学和临床意义。这项工作的目的是解决肌动蛋白在果蝇胚胎初级上皮细胞-细胞连接的组装/稳定性中所发挥的作用。具体来说，Nullo 是一种细胞-细胞连接蛋白，可以协调膜插入与连接处的肌动蛋白重塑，将使用高时间和空间分辨率共聚焦显微镜（3 维和 4 维）研究 Nullo 的功能。这项工作的目标是 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，2) 展示一种细胞机制，通过连接处的膜插入协调连接处的肌动蛋白重塑。