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

Detalhes bibliográficos
Autor(a) principal: Nolasco, S.
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/10400.5/23478
Resumo: Research Areas: Cell Biology ; Developmental Biology
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spelling Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB and TBCEColchicineTubulin cofactorsTBCATBCBTBCETubulin heterodimer dissociationMicrotubule cytoskeletonResearch Areas: Cell Biology ; Developmental BiologyColchicine 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 in 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 antimitotic 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 preexisting 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 MediaRepositório da Universidade de LisboaNolasco, S.Bellido, JavierSerna, MarinaCarmona, BrunoSoares, HelenaZabala, Juan Carlos2022-02-13T23:36:01Z2021-04-222021-04-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.5/23478engNolasco S, Bellido J, Serna M, Carmona B, Soares H, Zabala JC. 2021. Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB and TBCE. Frontiers in Cell and Developmental Biology, 9:656273. Doi: 10.3389/fcell.2021.6562732296-634X10.3389/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:RCAAP2023-03-06T14:53:03Zoai:www.repository.utl.pt:10400.5/23478Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:07:42.698120Repositório 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, S.
Colchicine
Tubulin cofactors
TBCA
TBCB
TBCE
Tubulin heterodimer dissociation
Microtubule cytoskeleton
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, S.
author_facet Nolasco, S.
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 Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Nolasco, S.
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
topic Colchicine
Tubulin cofactors
TBCA
TBCB
TBCE
Tubulin heterodimer dissociation
Microtubule cytoskeleton
description Research Areas: Cell Biology ; Developmental Biology
publishDate 2021
dc.date.none.fl_str_mv 2021-04-22
2021-04-22T00:00:00Z
2022-02-13T23:36:01Z
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/10400.5/23478
url http://hdl.handle.net/10400.5/23478
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. 2021. Colchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB and TBCE. Frontiers in Cell and Developmental Biology, 9:656273. Doi: 10.3389/fcell.2021.656273
2296-634X
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
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