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Research Project
Mechanism of centriole inheritance and maintenance
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Noncanonical Biogenesis of Centrioles and Basal Bodies
Publication . Nabais, Catarina; Pereira, Sónia Gomes; Bettencourt-Dias, Mónica
Centrioles and basal bodies (CBBs) organize centrosomes and cilia within eukaryotic cells. These organelles are composed of microtubules and hundreds of proteins performing multiple functions such as signaling, cytoskeleton remodeling, and cell motility. The CBB is present in all branches of the eukaryotic tree of life and, despite its ultrastructural and protein conservation, there is diversity in its function, occurrence (i.e., presence/absence), and modes of biogenesis across species. In this review, we provide an overview of the multiple pathways through which CBBs are formed in nature, with a special focus on the less studied, noncanonical ways. Despite the differences among each mechanism herein presented, we highlighted some of their common principles. These principles, governing different steps of biogenesis, ensure that CBBs may perform a multitude of functions in a huge diversity of organisms but yet retained their robustness in structure throughout evolution.
Maintaining centrosomes and cilia
Publication . Werner, Sascha; Pimenta-Marques, Ana; Bettencourt-Dias, Mónica
Centrosomes and cilia are present in organisms from all branches of the eukaryotic tree of life. These structures are composed of microtubules and various other proteins, and are required for a plethora of cell processes such as structuring the cytoskeleton, sensing the environment, and motility. Deregulation of centrosome and cilium components leads to a wide range of diseases, some of which are incompatible with life. Centrosomes and cilia are thought to be very stable and can persist over long periods of time. However, these structures can disappear in certain developmental stages and diseases. Moreover, some centrosome and cilia components are quite dynamic. While a large body of knowledge has been produced regarding the biogenesis of these structures, little is known about how they are maintained. In this Review, we propose the existence of specific centrosome and cilia maintenance programs, which are regulated during development and homeostasis, and when deregulated can lead to disease.
PLK4 is a microtubule-associated protein that self assembles promoting de novo MTOC formation
Publication . Gouveia, Susana Montenegro; Zitouni, Sihem; Kong, Dong; Duarte, Paulo; Gomes, Beatriz Ferreira; Sousa, Ana Laura; Tranfield, Erin M.; Hyman, Anthony; Loncarek, Jadranka; Bettencourt-Dias, Monica
The centrosome is an important microtubule-organizing centre (MTOC) in animal cells. It consists of two barrel-shaped structures, the centrioles, surrounded by the pericentriolar material (PCM), which nucleates microtubules. Centrosomes can form close to an existing structure (canonical duplication) or de novo How centrosomes form de novo is not known. The master driver of centrosome biogenesis, PLK4, is critical to recruit several centriole components. Here, we investigate the beginning of centrosome biogenesis, taking advantage of Xenopus egg extracts, where PLK4 can induce de novo MTOC formation (Eckerdt et al., 2011; Zitouni et al., 2016). Surprisingly, we observe that in vitro, PLK4 can self-assemble into condensates that recruit α/β-tubulin. In Xenopus extracts, PLK4 assemblies additionally recruit PLK4's substrate, STIL, and the microtubule nucleator, γ-tubulin, forming acentriolar MTOCs de novo The assembly of these robust microtubule asters is independent of dynein, similarly to centrosomes. We suggest a new mechanism of action for PLK4, where it forms a self-organizing catalytic scaffold that recruits centriole components, PCM factors and α/β-tubulin, leading to MTOC formation.
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Funding agency
European Commission
Funding programme
H2020
Funding Award Number
683258