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Centrosome positioning and development of ciliopathies: role of the human centrosomal protein TBCCD1

2019-11Conference object Open access
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dc.contributor.authorCarmona, Bruno
dc.contributor.authorCamelo, Carolina
dc.contributor.authorMehraz, Manon
dc.contributor.authorLemullois, Michel
dc.contributor.authorFerreira, David C.
dc.contributor.authorNolasco, Sofia
dc.contributor.authorLince-Faria, Mariana
dc.contributor.authorMarinho, H. Susana
dc.contributor.authorBettencourt-Dias, Mónica
dc.contributor.authorTassin, Anne-Marie
dc.contributor.authorSoares, Helena
dc.date.accessioned2020-06-11T11:16:26Z
dc.date.available2020-06-11T11:16:26Z
dc.date.issued2019-11
dc.descriptionProject IPL/2019/MOONOFCILI/ESTeSLpt_PT
dc.description.abstractAims/Context: Primary cilia are specialized microtubule-based signaling organelles that convey extracellular signaling and cellular polarity into a cellular response. Defects in primary cilia assembly/function cause severe diseases known as ciliopathies, typified by clinical manifestations, like infertility, obesity, brain problems, blindness, and kidney cysts. Primary cilia assembly entails centrosome migration to the plasma membrane where a centriole docks, maturates into a basal body (BB), and assembles the cilia axoneme. The human centrosomal TBCCD1 is a critical factor in centrosome positioning previously identified by us. Our aim is to discover the mechanisms/signals required for the correct positioning of the centrosome during cilia assembly, and how these mechanisms, when compromised, are related to ciliopathies. Methods: The proximity-dependent identification (BioID) assay was used to screen for TBCCD1 interactors. Immunofluorescent and super-resolution microscopy, as well as Western blot, were used to study the levels and cellular localization of the identified TBCCD1 interactors in human RPE1 cells overexpressing or depleted of TBCCD1. To study the impact of TBCCD1 knockdown in motile cilia the ciliate Paramecium, containing ∼3,000 motile cilia, was used. Results: Our BioID screen for TBCCD1 interactors identified several well-known proteins encoded by ciliopathy genes, e.g. the centrosomal protein OFD1 involved in the Orofacial-Digital Syndrome. We show that TBCCD1 knockdown and overexpression in RPE1 cells affects OFD1 distribution. Super-resolution microscopy shows TBCCD1 is localized at the distal region of the centrosome and that its depletion dramatically affects the centrosome subdistal protein CEP170, a component of cilia basal feet. In Paramecium, the TBCCD1 knockdown causes abnormal BB-associated structures organization and anomalous BB positioning/anchoring defects. Conclusions: Our data support a role for TBCCD1 in the maintenance of centrosome structure and in BB anchoring at the cell membrane during ciliogenesis. TBCCD1 is emerging as a novel protein with a role in human ciliopathies.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCarmona B, Camelo C, Mehraz M, Lemullois M, Nolasco S, Soares H, et al. Centrosome positioning and development of ciliopathies: role of the human centrosomal protein TBCCD1. In: 23rd Annual Meeting da Sociedade Portuguesa de Genética Humana, Fundação Bissaya Barreto, Bencanta (Coimbra), 14 a 16 de novembro de 2019. Proceedings of the 23rd Annual Meeting of the Portuguese Society of Human Genetics. Medicine. 2020;99(9):e19291.pt_PT
dc.identifier.doi10.1097/MD.0000000000019291pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/11823
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationProject IPL/2019/MOONOFCILI/ESTeSLpt_PT
dc.relation.publisherversionhttps://journals.lww.com/md-journal/fulltext/2020/02280/proceedings_of_the_23rd_annual_meeting_of_the.41.aspxpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectTBCCD1pt_PT
dc.subjectCiliopathy-involvedpt_PT
dc.subjectCiliapt_PT
dc.subjectOrofacio-digital syndromept_PT
dc.subjectIPL/2019/MOONOFCILI/ESTeSLpt_PT
dc.titleCentrosome positioning and development of ciliopathies: role of the human centrosomal protein TBCCD1pt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceCoimbrapt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT

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