Centriole Biogenesis: Symmetry Breaking and Site Selection

Ignacio, David P.; Coffman, Valerie C.; Dawes, Adriana T.

doi:10.1016/j.tcb.2018.11.001

Cited by 3 publications

(1 citation statement)

References 8 publications

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“…Moreover, Plk4 overexpression can promote de novo centriole assembly in acentriolar cells (Peel et al, 2007;Rodrigues-Martins et al, 2007). Due to its importance in centriole assembly, cells have evolved several regulatory mechanisms to restrict daughter centriole assembly to a single event per cell cycle and suppress ectopic Plk4 activity in order to prevent rampant centriole (and thus, centrosome) amplification (Chan, 2011;Ignacio et al, 2019;Sabat-Pośpiech et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Polo-like kinase 4 homodimerization is not required for catalytic activation, autodestruction, or centriole assembly

Ryniawec

Buster

Slevin

et al. 2021

Preprint

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Polo-like kinase 4 (Plk4) is the master-regulator of centriole assembly and cell cycle-dependent regulation of its activity maintains proper centrosome number. During most of the cell cycle, Plk4 levels are nearly undetectable due to its ability to autophosphorylate and trigger its own ubiquitin-mediated degradation. However, during mitotic exit, Plk4 forms a single aggregate on the centriole surface to stimulate centriole duplication. Whereas most Polo-like kinase family members are monomeric, Plk4 is unique because it forms homodimers. Notably, Plk4 trans-autophosphorylates a degron near its kinase domain, a critical step in autodestruction. While it is thought that the purpose of homodimerization is to promote trans-autophosphorylation, this has not been tested. Here, we generate separation-of-function Plk4 mutants that fail to dimerize, and we show that homodimerization is required to create a binding site for the Plk4 activator, Asterless. Surprisingly, Plk4 dimer mutants are catalytically active in cells, promote centriole assembly, and can trans-autophosphorylate by a process based its on concentration-dependent aggregation. Our findings implicate a concentration-dependent pathway of Plk4 activation that does not require Asterless binding or homodimerization. Lastly, we propose a model of Plk4 cell cycle regulation that utilizes both activation pathways – Asterless-dependent and aggregation-driven – to restrict centriole assembly to mother centrioles.

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Section: Introductionmentioning

confidence: 99%

Polo-like kinase 4 homodimerization is not required for catalytic activation, autodestruction, or centriole assembly

Ryniawec

Buster

Slevin

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

Cell shape

Adl

2025

Protistology

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Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly

Ryniawec

Buster

Slevin

et al. 2023

MBoC

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Polo-like kinase 4 (Plk4) is the master-regulator of centriole assembly and cell cycle-dependent regulation of its activity maintains proper centrosome number. During most of the cell cycle, Plk4 levels are nearly undetectable due to its ability to autophosphorylate and trigger its own ubiquitin-mediated degradation. However, during mitotic exit, Plk4 forms a single aggregate on the centriole surface to stimulate centriole duplication. Whereas most Polo-like kinase family members are monomeric, Plk4 is unique because it forms homodimers. Notably, Plk4 trans-autophosphorylates a degron near its kinase domain, a critical step in autodestruction. While it is thought that the purpose of homodimerization is to promote trans-autophosphorylation, this has not been tested. Here, we generated separation-of-function Plk4 mutants that fail to dimerize and show that homodimerization creates a binding site for the Plk4 activator, Asterless. Surprisingly however, Plk4 dimer mutants are catalytically-active in cells, promote centriole assembly, and can trans-autophosphorylate through concentration-dependent condensate formation. Moreover, we mapped and then deleted the weak-interacting regions within Plk4 that mediate condensation and conclude that dimerization and condensation are not required for centriole assembly. Our findings suggest that Plk4 dimerization and condensation function simply to downregulate Plk4 and suppress centriole overduplication. [Media: see text]

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Centriole Biogenesis: Symmetry Breaking and Site Selection

Cited by 3 publications

References 8 publications

Polo-like kinase 4 homodimerization is not required for catalytic activation, autodestruction, or centriole assembly

Polo-like kinase 4 homodimerization is not required for catalytic activation, autodestruction, or centriole assembly

Cell shape

Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly

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