Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE

Detalhes bibliográficos
Autor(a) principal: Nolasco, Sofia
Data de Publicação: 2021
Outros Autores: Bellido, Javier, Serna, Marina, Carmona, Bruno, Soares, Helena, Zabala, Juan Carlos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.21/13226
Resumo: FCT_Project UID/QUI/00100/2019
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spelling Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCEColchicineTubulin cofactorsTBCATBCBTBCETubulin heterodimer dissociationMicrotubule cytoskeletonProject UID/QUI/00100/2019Project UIDB/00276/2020FCT_Project UID/QUI/00100/2019FCT_Project UIDB/00276/2020Colchicine has been used to treat gout and, more recently, to effectively prevent autoinflammatory diseases and both primary and recurrent episodes of pericarditis. The anti-inflammatory action of colchicine seems to result from irreversible inhibition of tubulin polymerization and microtubule (MT) assembly by binding to the tubulin heterodimer, avoiding the signal transduction required to the activation of the entire NLRP3 inflammasome. Emerging results show that the MT network is a potential regulator of cardiac mechanics. Here, we investigated how colchicine impacts tubulin folding cofactors TBCA, TBCB, and TBCE activities. We show that TBCA is abundant in mouse heart insoluble protein extracts. Also, a decrease of the TBCA/β-tubulin complex followed by an increase of free TBCA is observed in human cells treated with colchicine. The presence of free TBCA is not observed in cells treated with other anti-mitotic agents such as nocodazole or cold shock, neither after translation inhibition by cycloheximide. In vitro assays show that colchicine inhibits tubulin heterodimer dissociation by TBCE/TBCB, probably by interfering with interactions of TBCE with tubulin dimers, leading to free TBCA. Manipulation of TBCA levels, either by RNAi or overexpression results in decreased levels of tubulin heterodimers. Together, these data strongly suggest that TBCA is mainly receiving β-tubulin from the dissociation of pre-existing heterodimers instead of newly synthesized tubulins. The TBCE/TBCB+TBCA system is crucial for controlling the critical concentration of free tubulin heterodimers and MT dynamics in the cells by recycling the tubulin heterodimers. It is conceivable that colchicine affects tubulin heterodimer recycling through the TBCE/TBCB+TBCA system producing the known benefits in the treatment of pericardium inflammation.Frontiers MediaRCIPLNolasco, SofiaBellido, JavierSerna, MarinaCarmona, BrunoSoares, HelenaZabala, Juan Carlos2021-04-22T17:05:25Z2021-042021-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/13226engNolasco S, Bellido J, Serna M, Carmona B, Soares H, Zabala JC. Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE. Front Cell Dev Biol. 2021;9:656273.10.3389/fcell.2021.656273info: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:RCAAP2023-08-03T10:07:36Zoai:repositorio.ipl.pt:10400.21/13226Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:21:12.947364Repositório 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 Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
title Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
spellingShingle Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
Nolasco, Sofia
Colchicine
Tubulin cofactors
TBCA
TBCB
TBCE
Tubulin heterodimer dissociation
Microtubule cytoskeleton
Project UID/QUI/00100/2019
Project UIDB/00276/2020
title_short Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
title_full Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
title_fullStr Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
title_full_unstemmed Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
title_sort Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE
author Nolasco, Sofia
author_facet Nolasco, Sofia
Bellido, Javier
Serna, Marina
Carmona, Bruno
Soares, Helena
Zabala, Juan Carlos
author_role author
author2 Bellido, Javier
Serna, Marina
Carmona, Bruno
Soares, Helena
Zabala, Juan Carlos
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv RCIPL
dc.contributor.author.fl_str_mv Nolasco, Sofia
Bellido, Javier
Serna, Marina
Carmona, Bruno
Soares, Helena
Zabala, Juan Carlos
dc.subject.por.fl_str_mv Colchicine
Tubulin cofactors
TBCA
TBCB
TBCE
Tubulin heterodimer dissociation
Microtubule cytoskeleton
Project UID/QUI/00100/2019
Project UIDB/00276/2020
topic Colchicine
Tubulin cofactors
TBCA
TBCB
TBCE
Tubulin heterodimer dissociation
Microtubule cytoskeleton
Project UID/QUI/00100/2019
Project UIDB/00276/2020
description FCT_Project UID/QUI/00100/2019
publishDate 2021
dc.date.none.fl_str_mv 2021-04-22T17:05:25Z
2021-04
2021-04-01T00:00:00Z
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 http://hdl.handle.net/10400.21/13226
url http://hdl.handle.net/10400.21/13226
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Nolasco S, Bellido J, Serna M, Carmona B, Soares H, Zabala JC. Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB, and TBCE. Front Cell Dev Biol. 2021;9:656273.
10.3389/fcell.2021.656273
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.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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
_version_ 1799133483030806528

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