Open AccessFAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
Author(s) -
Jianfeng Lin,
Thuc Vy Le,
Katherine Augspurger,
Douglas Tritschler,
Raqual Bower,
Gang Fu,
Catherine A. Perrone,
Eileen O’Toole,
Kristyn VanderWaal Mills,
Erin E. Dymek,
Elizabeth F. Smith,
Daniela Nicastro,
Mary E. Porter
Publication year - 2019
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e19-07-0367
Subject(s) - dynein , intraflagellar transport , cilium , biology , dynactin , axoneme , flagellum , microbiology and biotechnology , microtubule , motor protein , dynein atpase , ciliogenesis , motile cilium , genetics , gene
Ciliary motility depends on both the precise spatial organization of multiple dynein motors within the 96 nm axonemal repeat and the 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 preassembly 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 (IDAs) to a specific location in the 96 nm repeat. IDA8 encodes flagellar-associated polypeptide (FAP)57/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 IDAs and regulatory complexes.