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FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia

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 as...

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Autores principales: Lin, Jianfeng, Le, Thuc Vy, Augspurger, Katherine, Tritschler, Douglas, Bower, Raqual, Fu, Gang, Perrone, Catherine, O’Toole, Eileen T., Mills, Kristyn VanderWaal, Dymek, Erin, Smith, Elizabeth, Nicastro, Daniela, Porter, Mary E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761771/
https://www.ncbi.nlm.nih.gov/pubmed/31483737
http://dx.doi.org/10.1091/mbc.E19-07-0367
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author Lin, Jianfeng
Le, Thuc Vy
Augspurger, Katherine
Tritschler, Douglas
Bower, Raqual
Fu, Gang
Perrone, Catherine
O’Toole, Eileen T.
Mills, Kristyn VanderWaal
Dymek, Erin
Smith, Elizabeth
Nicastro, Daniela
Porter, Mary E.
author_facet Lin, Jianfeng
Le, Thuc Vy
Augspurger, Katherine
Tritschler, Douglas
Bower, Raqual
Fu, Gang
Perrone, Catherine
O’Toole, Eileen T.
Mills, Kristyn VanderWaal
Dymek, Erin
Smith, Elizabeth
Nicastro, Daniela
Porter, Mary E.
author_sort Lin, Jianfeng
collection PubMed
description 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.
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spelling pubmed-67617712019-12-16 FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia Lin, Jianfeng Le, Thuc Vy Augspurger, Katherine Tritschler, Douglas Bower, Raqual Fu, Gang Perrone, Catherine O’Toole, Eileen T. Mills, Kristyn VanderWaal Dymek, Erin Smith, Elizabeth Nicastro, Daniela Porter, Mary E. Mol Biol Cell Articles 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. The American Society for Cell Biology 2019-10-01 /pmc/articles/PMC6761771/ /pubmed/31483737 http://dx.doi.org/10.1091/mbc.E19-07-0367 Text en © 2019 Lin, Le, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Lin, Jianfeng
Le, Thuc Vy
Augspurger, Katherine
Tritschler, Douglas
Bower, Raqual
Fu, Gang
Perrone, Catherine
O’Toole, Eileen T.
Mills, Kristyn VanderWaal
Dymek, Erin
Smith, Elizabeth
Nicastro, Daniela
Porter, Mary E.
FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
title FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
title_full FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
title_fullStr FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
title_full_unstemmed FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
title_short FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
title_sort fap57/wdr65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761771/
https://www.ncbi.nlm.nih.gov/pubmed/31483737
http://dx.doi.org/10.1091/mbc.E19-07-0367
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