Rab35 controls cilium length, function and membrane composition

Detalhes bibliográficos
Autor(a) principal: Kuhns, Stefanie
Data de Publicação: 2019
Outros Autores: Seixas, Cecília, Pestana, Sara, Tavares, Bárbara, Nogueira, Renata, Jacinto, Raquel, Ramalho, José S., Simpson, Jeremy C., Andersen, Jens S., Echard, Arnaud, Lopes, Susana S., Barral, Duarte C., Blacque, Oliver E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/140388
Resumo: 8021-00425B) to JSA, by a postdoctoral fellowship from FCT (SFRH/BPD/32323/2006) to CS and by iNOVA4Health—UID/Multi/ 04462/2013, a program financially supported by FCT/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. This article is supported by the LYSOCIL project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 811087.
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spelling Rab35 controls cilium length, function and membrane compositionArl13bcilialeft-right asymmetryRab35SmoothenedBiochemistryMolecular BiologyGenetics8021-00425B) to JSA, by a postdoctoral fellowship from FCT (SFRH/BPD/32323/2006) to CS and by iNOVA4Health—UID/Multi/ 04462/2013, a program financially supported by FCT/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. This article is supported by the LYSOCIL project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 811087.Rab and Arl guanine nucleotide-binding (G) proteins regulate trafficking pathways essential for the formation, function and composition of primary cilia, which are sensory devices associated with Sonic hedgehog (Shh) signalling and ciliopathies. Here, using mammalian cells and zebrafish, we uncover ciliary functions for Rab35, a multitasking G protein with endocytic recycling, actin remodelling and cytokinesis roles. Rab35 loss via siRNAs, morpholinos or knockout reduces cilium length in mammalian cells and the zebrafish left-right organiser (Kupffer's vesicle) and causes motile cilia-associated left-right asymmetry defects. Consistent with these observations, GFP-Rab35 localises to cilia, as do GEF (DENND1B) and GAP (TBC1D10A) Rab35 regulators, which also regulate ciliary length and Rab35 ciliary localisation. Mammalian Rab35 also controls the ciliary membrane levels of Shh signalling regulators, promoting ciliary targeting of Smoothened, limiting ciliary accumulation of Arl13b and the inositol polyphosphate 5-phosphatase (INPP5E). Rab35 additionally regulates ciliary PI(4,5)P2 levels and interacts with Arl13b. Together, our findings demonstrate roles for Rab35 in regulating cilium length, function and membrane composition and implicate Rab35 in pathways controlling the ciliary levels of Shh signal regulators.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNKuhns, StefanieSeixas, CecíliaPestana, SaraTavares, BárbaraNogueira, RenataJacinto, RaquelRamalho, José S.Simpson, Jeremy C.Andersen, Jens S.Echard, ArnaudLopes, Susana S.Barral, Duarte C.Blacque, Oliver E.2022-06-20T22:19:14Z2019-10-042019-10-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/140388eng1469-221XPURE: 14555932https://doi.org/10.15252/embr.201847625info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:17:31Zoai:run.unl.pt:10362/140388Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:49:38.512288Repositório 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 Rab35 controls cilium length, function and membrane composition
title Rab35 controls cilium length, function and membrane composition
spellingShingle Rab35 controls cilium length, function and membrane composition
Kuhns, Stefanie
Arl13b
cilia
left-right asymmetry
Rab35
Smoothened
Biochemistry
Molecular Biology
Genetics
title_short Rab35 controls cilium length, function and membrane composition
title_full Rab35 controls cilium length, function and membrane composition
title_fullStr Rab35 controls cilium length, function and membrane composition
title_full_unstemmed Rab35 controls cilium length, function and membrane composition
title_sort Rab35 controls cilium length, function and membrane composition
author Kuhns, Stefanie
author_facet Kuhns, Stefanie
Seixas, Cecília
Pestana, Sara
Tavares, Bárbara
Nogueira, Renata
Jacinto, Raquel
Ramalho, José S.
Simpson, Jeremy C.
Andersen, Jens S.
Echard, Arnaud
Lopes, Susana S.
Barral, Duarte C.
Blacque, Oliver E.
author_role author
author2 Seixas, Cecília
Pestana, Sara
Tavares, Bárbara
Nogueira, Renata
Jacinto, Raquel
Ramalho, José S.
Simpson, Jeremy C.
Andersen, Jens S.
Echard, Arnaud
Lopes, Susana S.
Barral, Duarte C.
Blacque, Oliver E.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Kuhns, Stefanie
Seixas, Cecília
Pestana, Sara
Tavares, Bárbara
Nogueira, Renata
Jacinto, Raquel
Ramalho, José S.
Simpson, Jeremy C.
Andersen, Jens S.
Echard, Arnaud
Lopes, Susana S.
Barral, Duarte C.
Blacque, Oliver E.
dc.subject.por.fl_str_mv Arl13b
cilia
left-right asymmetry
Rab35
Smoothened
Biochemistry
Molecular Biology
Genetics
topic Arl13b
cilia
left-right asymmetry
Rab35
Smoothened
Biochemistry
Molecular Biology
Genetics
description 8021-00425B) to JSA, by a postdoctoral fellowship from FCT (SFRH/BPD/32323/2006) to CS and by iNOVA4Health—UID/Multi/ 04462/2013, a program financially supported by FCT/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. This article is supported by the LYSOCIL project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 811087.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-04
2019-10-04T00:00:00Z
2022-06-20T22:19:14Z
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 http://hdl.handle.net/10362/140388
url http://hdl.handle.net/10362/140388
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1469-221X
PURE: 14555932
https://doi.org/10.15252/embr.201847625
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
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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