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PLK4 is a microtubule-associated protein that self assembles promoting de novo MTOC formation

View ORCID ProfileSusana Montenegro Gouveia, Sihem Zitouni, Dong Kong, Paulo Duarte, Beatriz Ferreira Gomes, Ana Laura Sousa, Erin M. Tranfield, Antony Hyman, Jadranka Loncarek, View ORCID ProfileMonica Bettencourt-Dias
doi: https://doi.org/10.1101/312272
Susana Montenegro Gouveia
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780–156, Portugal
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  • ORCID record for Susana Montenegro Gouveia
  • For correspondence: susanamgouveia@gmail.com mdias@igc.gulbenkian.pt
Sihem Zitouni
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780–156, Portugal
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  • For correspondence: susanamgouveia@gmail.com mdias@igc.gulbenkian.pt
Dong Kong
Laboratory of Protein Dynamics and Signaling, National Institutes of Health/Center for Cancer Research/National Cancer Institute-Frederick, Frederick, MD
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Paulo Duarte
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780–156, Portugal
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Beatriz Ferreira Gomes
Max Planck Institute of Molecular Biology and Genetics, Pfotenhauerstrasse 108 01307 Dresden, Germany
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Ana Laura Sousa
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780–156, Portugal
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Erin M. Tranfield
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780–156, Portugal
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Antony Hyman
Max Planck Institute of Molecular Biology and Genetics, Pfotenhauerstrasse 108 01307 Dresden, Germany
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Jadranka Loncarek
Laboratory of Protein Dynamics and Signaling, National Institutes of Health/Center for Cancer Research/National Cancer Institute-Frederick, Frederick, MD
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Monica Bettencourt-Dias
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  • ORCID record for Monica Bettencourt-Dias
  • For correspondence: susanamgouveia@gmail.com mdias@igc.gulbenkian.pt
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Summary statement

PLK4 binds to microtubules and self assembles into supramolecular assemblies that recruit tubulin and trigger de novo MTOC formation in Xenopus laevis extracts.

Abstract The centrosome is an important microtubule-organizing center (MTOCs) in animal cells and it consists of two barrel-shaped structures (centrioles), surrounded by the pericentriolar material (PCM), which nucleates microtubules. PCM components form condensates, supramolecular assemblies that concentrate microtubule nucleators. Centrosomes can form close to an existing structure (canonical duplication) or de novo. How centrosomes form de novo is not known. PLK4 is a master driver of centrosome biogenesis, which is critical to recruit several centriole components. Here, we investigate the beginning of centrosome biogenesis, taking advantage of Xenopus egg extracts, where we and others have shown that 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 supramolecular assemblies that recruit α/β-tubulin. In Xenopus extracts, PLK4 supramolecular assemblies additionally recruit the PLK4 substrate STIL and the microtubule nucleator, γ-tubulin, and form 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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  • * Co-first author

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Posted May 01, 2018.
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PLK4 is a microtubule-associated protein that self assembles promoting de novo MTOC formation
Susana Montenegro Gouveia, Sihem Zitouni, Dong Kong, Paulo Duarte, Beatriz Ferreira Gomes, Ana Laura Sousa, Erin M. Tranfield, Antony Hyman, Jadranka Loncarek, Monica Bettencourt-Dias
bioRxiv 312272; doi: https://doi.org/10.1101/312272
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PLK4 is a microtubule-associated protein that self assembles promoting de novo MTOC formation
Susana Montenegro Gouveia, Sihem Zitouni, Dong Kong, Paulo Duarte, Beatriz Ferreira Gomes, Ana Laura Sousa, Erin M. Tranfield, Antony Hyman, Jadranka Loncarek, Monica Bettencourt-Dias
bioRxiv 312272; doi: https://doi.org/10.1101/312272

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