WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing

Detalhes bibliográficos
Autor(a) principal: De-Castro, ARG
Data de Publicação: 2022
Outros Autores: Rodrigues, DRM, De-Castro, MJG, Vieira, N, Vieira, C, Carvalho, AX, Gassmann, R, Abreu, CMC, Dantas, T
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/137827
Resumo: The dynein-2 motor complex drives retrograde intraflagellar transport (IFT), playing a pivotal role in the assembly and functions of cilia. However, the mechanisms that regulate dynein-2 motility remain poorly understood. Here, we identify the Caenorhabditis elegans WDR60 homologue, WDR-60, and dissect the roles of this intermediate chain using genome editing and live imaging of endogenous dynein-2/IFT components. We find that loss of WDR-60 impairs dynein-2 recruitment to cilia and its incorporation onto anterograde IFT trains, reducing retrograde motor availability at the ciliary tip. Consistent with this, we show that fewer dynein-2 motors power WDR-60-deficient retrograde IFT trains, which move at reduced velocities and fail to exit cilia, accumulating on the distal side of the transition zone. Remarkably, disrupting the transition zone's NPHP module almost fully restores ciliary exit of underpowered retrograde trains in wdr-60 mutants. This work establishes WDR-60 as a major contributor to IFT, and the NPHP module as a roadblock to dynein-2 passage through the transition zone.
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spelling WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossingCiliaCytoskeletonDevelopmentGeneticsThe dynein-2 motor complex drives retrograde intraflagellar transport (IFT), playing a pivotal role in the assembly and functions of cilia. However, the mechanisms that regulate dynein-2 motility remain poorly understood. Here, we identify the Caenorhabditis elegans WDR60 homologue, WDR-60, and dissect the roles of this intermediate chain using genome editing and live imaging of endogenous dynein-2/IFT components. We find that loss of WDR-60 impairs dynein-2 recruitment to cilia and its incorporation onto anterograde IFT trains, reducing retrograde motor availability at the ciliary tip. Consistent with this, we show that fewer dynein-2 motors power WDR-60-deficient retrograde IFT trains, which move at reduced velocities and fail to exit cilia, accumulating on the distal side of the transition zone. Remarkably, disrupting the transition zone's NPHP module almost fully restores ciliary exit of underpowered retrograde trains in wdr-60 mutants. This work establishes WDR-60 as a major contributor to IFT, and the NPHP module as a roadblock to dynein-2 passage through the transition zone.Rockefeller University Press2022-01-032022-01-03T00:00:00Z2022-07-03T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/137827eng0021-952510.1083/jcb.202010178De-Castro, ARGRodrigues, DRMDe-Castro, MJGVieira, NVieira, CCarvalho, AXGassmann, RAbreu, CMCDantas, Tinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T15:47:18Zoai:repositorio-aberto.up.pt:10216/137827Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:32:12.118286Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
title WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
spellingShingle WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
De-Castro, ARG
Cilia
Cytoskeleton
Development
Genetics
title_short WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
title_full WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
title_fullStr WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
title_full_unstemmed WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
title_sort WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
author De-Castro, ARG
author_facet De-Castro, ARG
Rodrigues, DRM
De-Castro, MJG
Vieira, N
Vieira, C
Carvalho, AX
Gassmann, R
Abreu, CMC
Dantas, T
author_role author
author2 Rodrigues, DRM
De-Castro, MJG
Vieira, N
Vieira, C
Carvalho, AX
Gassmann, R
Abreu, CMC
Dantas, T
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv De-Castro, ARG
Rodrigues, DRM
De-Castro, MJG
Vieira, N
Vieira, C
Carvalho, AX
Gassmann, R
Abreu, CMC
Dantas, T
dc.subject.por.fl_str_mv Cilia
Cytoskeleton
Development
Genetics
topic Cilia
Cytoskeleton
Development
Genetics
description The dynein-2 motor complex drives retrograde intraflagellar transport (IFT), playing a pivotal role in the assembly and functions of cilia. However, the mechanisms that regulate dynein-2 motility remain poorly understood. Here, we identify the Caenorhabditis elegans WDR60 homologue, WDR-60, and dissect the roles of this intermediate chain using genome editing and live imaging of endogenous dynein-2/IFT components. We find that loss of WDR-60 impairs dynein-2 recruitment to cilia and its incorporation onto anterograde IFT trains, reducing retrograde motor availability at the ciliary tip. Consistent with this, we show that fewer dynein-2 motors power WDR-60-deficient retrograde IFT trains, which move at reduced velocities and fail to exit cilia, accumulating on the distal side of the transition zone. Remarkably, disrupting the transition zone's NPHP module almost fully restores ciliary exit of underpowered retrograde trains in wdr-60 mutants. This work establishes WDR-60 as a major contributor to IFT, and the NPHP module as a roadblock to dynein-2 passage through the transition zone.
publishDate 2022
dc.date.none.fl_str_mv 2022-01-03
2022-01-03T00:00:00Z
2022-07-03T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/137827
url https://hdl.handle.net/10216/137827
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-9525
10.1083/jcb.202010178
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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