F-Actin Remodeling at Newly Forming Cell-Cell Junctions

描述（由申请人提供）： 上皮细胞片层驱动形态发生，并且在成人组织中，完整的上皮细胞在组织隔室之间提供主动屏障。这些功能需要上皮细胞被极化，并且这种极性取决于细胞与细胞和细胞与基质的粘附。细胞-细胞粘附的丧失导致几种人类疾病，包括退行性皮肤起泡疾病、囊性肾病和癌症。 事实上，减少的细胞粘附与恶性细胞的侵袭性直接相关;并且癌的侵袭性通过挽救细胞-细胞粘附来抵消。鉴于上皮细胞的正常和病理生理的细胞-细胞粘附的必要性，了解细胞-细胞连接是如何组装和维持的具有生物学和临床意义。本研究的目的是探讨肌动蛋白在果蝇胚胎原代上皮细胞间连接的组装/稳定性中所起的作用。 具体而言，Nullo，细胞-细胞连接蛋白，可以协调膜插入与肌动蛋白在交界处重塑的功能，将使用高时间和空间分辨率共聚焦显微镜（3维和4维）进行研究。这项工作的目标是：1）在这个模型系统中，描述细胞-细胞连接的组装/维持与肌动蛋白动力学的关系，2）证明连接处的膜插入协调连接处的肌动蛋白重塑的细胞机制。

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.