PLK4 drives centriole amplification and apical surface area expansion in multiciliated cells

LoMastro, Gina M.; Drown, Chelsea G; Maryniak, Aubrey L; Jewett, Cayla E.; Strong, Margaret A.; Holland, Andrew J.

doi:10.1101/2022.06.06.494981

Cited by 2 publications

(1 citation statement)

References 55 publications

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“…proved that proteins that control cell cycle progression are also essential to drive multiciliated cell differentiation (Al Jord et al, 2017). Very recently, it was suggested that PLK4 protein and its kinase activity are essential for centriole amplification in multiciliated cells (LoMastro et al, 2022). These results corroborate the idea that the initial stages of centriole assembly are conserved between cycling and multiciliated cells.…”

Section: Discussionmentioning

confidence: 99%

McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation

Arbi

Skamnelou

Bournaka

et al. 2022

Preprint

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The centriole duplication cycle must be tightly controlled and coordinated with the chromosome cycle. Aberrations in centriole biogenesis can lead to cancer, developmental disorders and ciliopathies. Here, we show that McIdas -previously implicated in cell cycle control and centriole amplification in multiciliated cells- is critical to maintain centriole numbers. Using expansion microscopy, we demonstrate that McIdas is present at the middle part of centrioles, where it exhibits a differential localization during the cell cycle. McIdas loss perturbs daughter centriole biogenesis and centrosomal SAS6 recruitment, whereas its overexpression induces centriole overduplication. Consistently, McIdas depletion reduces PLK4-induced centriole amplification. McIdas interacts with and is phosphorylated by PLK4 in multiple sites identified by mass spectrometry. Mutational analysis shows that McIdas phosphorylation is important for centriole number control. Overall, our results identify a novel, direct role of McIdas on centriole duplication that can link its previously characterized roles in the chromosome cycle and multiciliogenesis.

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Section: Discussionmentioning

confidence: 99%

McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation

Arbi

Skamnelou

Bournaka

et al. 2022

Preprint

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Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins

Ozcan,

Kalkan,

Cicek

et al. 2024

Sci Rep

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Centrosome amplification is a hallmark of cancer and PLK4 is one of the responsible factors for cancer associated centrosome amplification. Increased PLK4 levels was also shown to contribute to generation of cells with centriole amplification in mammalian tissues as olfactory neuron progenitor cells. PLK4 overexpression generates centriole rosette (CR) structures which harbor more than two centrioles each. Long term PLK4 overexpression results with centrosome amplification, but the maturation of amplified centrioles in CRs and linking of PLK4 induced amplified centrosomes has not yet been investigated in detail. Here, we show evidence for generation of large clustered centrosomes which have more than 2 centriole rosettes and define these structures as centriole rosette clusters (CRCs) in cells that have high PLK4 levels for 2 consecutive cell cycles. In addition, we show that PLK4 induced CRs follow normal centrosomal maturation processes and generate CRC structures that are inter-connected with canonical centrosomal linker proteins as C-Nap1, Rootletin and Cep68 in the second cell cycle after PLK4 induction. Increased PLK4 levels in cells with C-Nap1 and Rootletin knock-out resulted with distanced CRs and CRCs in interphase, while Nek2 knock-out inhibited separation of CRCs in prometaphase, providing functional evidence for the binding of CRC structures with centrosomal linker proteins. Taken together, these results suggest a cell cycle dependent model for PLK4 induced centrosome amplification which occurs in 2 consecutive cell cycles: (i) CR state in the first cell cycle, and (ii) CRC state in the second cell cycle.

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PLK4 drives centriole amplification and apical surface area expansion in multiciliated cells

Cited by 2 publications

References 55 publications

McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation

McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation

Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins

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