The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels

Centriole duplication is tightly controlled to maintain correct centriole number through the cell cycle. A key component of this control is the regulated degradation of PLK4, the master regulator of centriole duplication. Here we show that the Rac1 guanine nucleotide exchange factor (GEF) Tiam1 loca...

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Bibliographic Details
Published inbioRxiv
Main Authors Porter, Andrew Phillip, White, Gavin R M, Erinn-Lee Ogg, Whalley, Helen J, Malliri, Angeliki
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.05.2020
Subjects
Anaphase
Aneuploidy
Cell cycle
Centrosomes
Chromosomes
F-box protein
Guanine
Guanine nucleotide exchange factor
Rac1 protein
Tiam1 protein
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Summary:Centriole duplication is tightly controlled to maintain correct centriole number through the cell cycle. A key component of this control is the regulated degradation of PLK4, the master regulator of centriole duplication. Here we show that the Rac1 guanine nucleotide exchange factor (GEF) Tiam1 localises to centrosomes during S-phase, where it is required for maintenance of normal centriole number. Depletion of Tiam1 leads to an increase in centrosomal PLK4, centriole overduplication and ultimately to lagging chromosomes at anaphase and aneuploidy. The effects of Tiam1 depletion can be rescued by re-expression of wild-type Tiam1 and catalytically inactive (GEF*) Tiam1, but not by Tiam1 mutants unable to bind to the F-box protein βTRCP, implying that Tiam1 regulates PLK4 levels through promoting βTRCP-mediated degradation. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.05.20.106120