High-resolution structural and global signaling network identification of the NEPH-NEPHRIN protein complex (A03)

NEPH-NEPHRIN 蛋白复合物 (A03) 的高分辨率结构和整体信号网络鉴定

• 批准号: 267104821
• 金额: --
• 依托单位: III. Medizinische Klinik und Poliklinik (Nephrologie, Rheumatologie - Nierentransplantation - Sektion Endokrinologie/Diabetologie)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/267104821?language=en
• 关键词: resolution; structural; global; signaling; network

We established a multispecies platform of complementary transgenic mice with floxed genes for Nphs1, Neph1, Neph2 and Neph3, as well as Gallus gallus and Drosophila model systems that will be combined with high-resolution, large-scale serial 3D EM reconstructions and functional studies to unravel the structure and function of the NEPH-NEPHRIN complex at the slit diaphragm (SD). This will provide the foundation to: (1) Correlate the high-resolution 3D structure of SDs. (2) Analyze the precise role of all NEPH-NEPHRIN family members for the development, stability, dynamics and maintenance of the SD, and (3) Systematically decode the global signaling network of the NEPH-NEPHRIN complex by using a genome-wide RNAi suppressor screen in Drosophila nephrocytes.

我们建立了一个具有nph1、Neph1、Neph2和Neph3固定基因的互补转基因小鼠的多物种平台，以及Gallus Gallus和果蝇模型系统，将结合高分辨率、大规模序列3D EM重建和功能研究来揭示裂隙膈（SD）处nephi - nephrin复合物的结构和功能。这将为：(1)关联SDs的高分辨率三维结构提供基础。(2)分析所有nephi - nephrin家族成员在SD的发育、稳定、动态和维持中的确切作用；(3)利用果蝇肾细胞全基因组RNAi抑制因子筛选，系统解码nephi - nephrin复合物的全球信号网络。