FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
Abstract Ciliary motility depends on both the precise spatial organization of multiple dynein motors within the 96 nm axonemal repeat, and highly coordinated interactions between different dyneins and regulatory complexes located at the base of the radial spokes. Mutations in genes encoding cytoplasmic assembly factors, intraflagellar transport factors, docking proteins, dynein subunits, and associated regulatory proteins can all lead to defects in dynein assembly and ciliary motility. Significant progress has been made in the identification of dynein subunits and extrinsic factors required for pre-assembly of dynein complexes in the cytoplasm, but less is known about the docking factors that specify the unique binding sites for the different dynein isoforms on the surface of the doublet microtubules. We have used insertional mutagenesis to identify a new locus, IDA8/BOP2, required for targeting the assembly of a subset of inner dynein arms to a specific location in the 96 nm repeat. IDA8 encodes FAP57/WDR65, a highly conserved WD repeat, coiled coil domain protein. Using high resolution proteomic and structural approaches, we find that FAP57 forms a discrete complex. Cryo-electron tomography coupled with epitope tagging and gold labeling reveal that FAP57 forms an extended structure that interconnects multiple inner dynein arms and regulatory complexes.
Le Thuc Vy、Augspurger Katherine、Tritschler Douglas、Dymek Erin、Smith Elizabeth、Nicastro Daniela、Mills Kristyn VanderWaal、Bower Raqual、O?ˉToole Eileen T.、Porter Mary E.、Lin Jianfeng、Perrone Catherine、Fu Gang
Department of Genetics, Cell Biology and Development, University of MinnesotaDepartment of Genetics, Cell Biology and Development, University of MinnesotaDepartment of Genetics, Cell Biology and Development, University of MinnesotaDepartment of Biological Sciences, Class of 1978 Life Sciences Center Dartmouth CollegeDepartment of Biological Sciences, Class of 1978 Life Sciences Center Dartmouth CollegeDepartments of Cell Biology and Biophysics, University of Texas Southwestern Medical CenterDepartment of Genetics, Cell Biology and Development, University of MinnesotaDepartment of Genetics, Cell Biology and Development, University of MinnesotaDepartment of Molecular, Cellular, and Developmental Biology, University of ColoradoDepartment of Genetics, Cell Biology and Development, University of MinnesotaDepartments of Cell Biology and Biophysics, University of Texas Southwestern Medical CenterDepartment of Genetics, Cell Biology and Development, University of MinnesotaDepartments of Cell Biology and Biophysics, University of Texas Southwestern Medical Center
细胞生物学分子生物学生物科学研究方法、生物科学研究技术
Le Thuc Vy,Augspurger Katherine,Tritschler Douglas,Dymek Erin,Smith Elizabeth,Nicastro Daniela,Mills Kristyn VanderWaal,Bower Raqual,O?ˉToole Eileen T.,Porter Mary E.,Lin Jianfeng,Perrone Catherine,Fu Gang.FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia[EB/OL].(2025-03-28)[2025-05-22].https://www.biorxiv.org/content/10.1101/688291.点此复制
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