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

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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.