Analysis of the Drosophila Gene Rhomboid

小行星9318242 该提案的目标是了解菱形（rho）基因的功能，该基因是几个不同的发育事件所需的，包括：果蝇胚胎中早期背腹图案的形成，胚胎感觉器官的形成，以及成年翅静脉的形成。rho是形成这些不同结构所需的几种基因（称为腹侧群基因）之一。其他腹外侧组基因编码EGF/TGF α型生长因子（spitz）和果蝇EGF受体（egf-r）。rho是以空间定位模式表达的腹外侧组基因的唯一已知成员，该模式对应于需要腹外侧组基因活性的细胞。rho编码一种膜蛋白（Rho），并可能通过响应结合Spitz生长因子而放大EGF-R信号传导而起作用。由于EGF-R信号通路在进化过程中高度保守，因此这些在果蝇中的研究可能与其他物种（包括人类）直接相关。以下是本提案的具体研究目标：1）确定Rho蛋白的亚细胞定位。Rho蛋白是否如蛋白质作为受体复合物的一部分所预测的那样位于细胞表面？Rho是否位于细胞间的紧密接触部位？2)研究Rho蛋白的生物化学功能，并确定Rho是否与其他蛋白质发生物理相互作用。Rho蛋白是否与其他蛋白质（例如EGF-R信号通路的组分）发生物理相互作用？Spi是EGF-R的配体吗？Rho介导细胞粘附差异吗？3)确定rho是否致力于放大Spi-EGF-R信号传导或其他信号传导途径也被Rho激活？EGF-R通路的转录下调依赖于rho吗？ ***

9318242 Bier The goal of this proposal is to understand the function of the rhomboid (rho) gene that is required for several distinct developmental events including : early dorsal- ventral pattern formation in the Drosophila embryo, the formation of embryonic sensory organs, and the formation of adult wing veins. rho is one of several genes (referred to as ventro-lateral group genes) required for the formation of these diverse structures. Other ventro-lateral group genes encode an EGF/TGF alpha type of growth factor (spitz) and the Drosophila EGF-receptor (egf-r). rho is the only known member of the ventro-lateral group of genes expressed in a spatially localized pattern corresponding to the cells requiring the activity of ventro-lateral group genes. rho encodes a membrane protein (Rho) and may act by amplifying EGF-R signaling in response to binding the Spitz growth factor. Because the EGF-R signaling pathway has been highly conserved during evolution it is likely that these studies in Drosophila will be directly relevant to other species, including humans. The following are specific research goals for this proposal: 1) Determine the subcellular localization of the Rho protein. Is the Rho protein located on the cell surface as predicted for a protein functioning as part of a receptor complex? Is Rho located at sites of intimate cell- cell contact? 2) Investigate how the Rho protein functions biochemically and determine whether Rho physically interacts with other proteins. Does the Rho protein physically interact with other proteins (e.g. components of the EGF-R signaling pathway)? Is Spi a ligand for EGF-R? Does Rho mediate differential cell adhesion? 3) Determine whether rho is dedicated to amplifying Spi-EGF-R signaling or are other signaling pathways also activated by Rho? Does transcriptional down regulation of components of the EGF-R pathway depend on rho? ***