An autonomous oscillator times and executes centriole biogenesis

The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a preexisting mother. Here we show that Plk4 forms an adaptive oscillator...

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Main Authors: Aydogan, MG, Steinacker, TL, Mofatteh, M, Gartenmann, L, Wainman, A, Saurya, S, Wong, SS, Zhou, FY, Boemo, MA, Raff, JW
Format: Journal article
Published: Cold Spring Harbor Laboratory 2019
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author Aydogan, MG
Steinacker, TL
Mofatteh, M
Gartenmann, L
Wainman, A
Saurya, S
Wong, SS
Zhou, FY
Boemo, MA
Raff, JW
author_facet Aydogan, MG
Steinacker, TL
Mofatteh, M
Gartenmann, L
Wainman, A
Saurya, S
Wong, SS
Zhou, FY
Boemo, MA
Raff, JW
author_sort Aydogan, MG
collection OXFORD
description The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a preexisting mother. Here we show that Plk4 forms an adaptive oscillator at the base of the growing centriole to initiate and time centriole biogenesis, ensuring that centrioles grow at the right time and to the right size. The Plk4 oscillator is normally entrained to the cell-cycle oscillator, but can run autonomously of it – explaining how centrioles can duplicate independently of cell cycle progression under certain conditions. Mathematical modelling indicates that this autonomously oscillating system is generated by a time-delayed negative-feedback loop in which Plk4 inactivates its centriolar receptor through multiple rounds of phosphorylation. We postulate that such organelle-specific autonomous oscillators could regulate the timing and execution of organelle biogenesis more generally.
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spelling oxford-uuid:43dac625-3908-4c5b-9d42-3b3ef010a69b2022-03-26T14:58:02ZAn autonomous oscillator times and executes centriole biogenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:43dac625-3908-4c5b-9d42-3b3ef010a69bSymplectic Elements at OxfordCold Spring Harbor Laboratory2019Aydogan, MGSteinacker, TLMofatteh, MGartenmann, LWainman, ASaurya, SWong, SSZhou, FYBoemo, MARaff, JWThe accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a preexisting mother. Here we show that Plk4 forms an adaptive oscillator at the base of the growing centriole to initiate and time centriole biogenesis, ensuring that centrioles grow at the right time and to the right size. The Plk4 oscillator is normally entrained to the cell-cycle oscillator, but can run autonomously of it – explaining how centrioles can duplicate independently of cell cycle progression under certain conditions. Mathematical modelling indicates that this autonomously oscillating system is generated by a time-delayed negative-feedback loop in which Plk4 inactivates its centriolar receptor through multiple rounds of phosphorylation. We postulate that such organelle-specific autonomous oscillators could regulate the timing and execution of organelle biogenesis more generally.
spellingShingle Aydogan, MG
Steinacker, TL
Mofatteh, M
Gartenmann, L
Wainman, A
Saurya, S
Wong, SS
Zhou, FY
Boemo, MA
Raff, JW
An autonomous oscillator times and executes centriole biogenesis
title An autonomous oscillator times and executes centriole biogenesis
title_full An autonomous oscillator times and executes centriole biogenesis
title_fullStr An autonomous oscillator times and executes centriole biogenesis
title_full_unstemmed An autonomous oscillator times and executes centriole biogenesis
title_short An autonomous oscillator times and executes centriole biogenesis
title_sort autonomous oscillator times and executes centriole biogenesis
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