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

2021-04-22Artigo científico Acesso aberto
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dc.contributor.authorNolasco, S.
dc.contributor.authorBellido, Javier
dc.contributor.authorSerna, Marina
dc.contributor.authorCarmona, Bruno
dc.contributor.authorSoares, Helena
dc.contributor.authorZabala, Juan Carlos
dc.date.accessioned2022-02-13T23:36:01Z
dc.date.available2022-02-13T23:36:01Z
dc.date.issued2021-04-22
dc.descriptionResearch Areas: Cell Biology ; Developmental Biologypt_PT
dc.description.abstractColchicine 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNolasco 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.2021.656273pt_PT
dc.identifier.doi10.3389/fcell.2021.656273pt_PT
dc.identifier.issn2296-634X
dc.identifier.urihttp://hdl.handle.net/10400.5/23478
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Mediapt_PT
dc.relationBFU2010-18948pt_PT
dc.relationCentro de Química Estrutural
dc.relationCentre for Interdisciplinary Research in Animal Health
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fcell.2021.656273/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectColchicinept_PT
dc.subjectTubulin cofactorspt_PT
dc.subjectTBCApt_PT
dc.subjectTBCBpt_PT
dc.subjectTBCEpt_PT
dc.subjectTubulin heterodimer dissociationpt_PT
dc.subjectMicrotubule cytoskeletonpt_PT
dc.titleColchicine blocks tubulin heterodimer recycling by tubulin cofactors TBCA, TBCB and TBCEpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentro de Química Estrutural
oaire.awardTitleCentre for Interdisciplinary Research in Animal Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F00100%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00276%2F2020/PT
oaire.citation.conferencePlaceLausanne, Switzerlandpt_PT
oaire.citation.titleFrontiers in Cell and Developmental Biologypt_PT
oaire.citation.volumeVol.9:656273pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameNolasco
person.givenNameSofia
person.identifier.ciencia-id5017-368D-3F71
person.identifier.orcid0000-0003-2168-0511
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscovery9e889432-c1ce-4e28-8e62-e6ab56601068
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