Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly

Siu Shing Wong; Zachary M. Wilmott; Saroj Saurya; Ines Alvarez-Rodrigo; Felix Y. Zhou; Kwai Yin Chau; Alain Goriely; Jordan W. Raff

doi:10.15252/embj.2022110891

Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly

Siu Shing Wong, Zachary M. Wilmott, Saroj Saurya, Ines Alvarez-Rodrigo, Felix Y. Zhou, Kwai Yin Chau, Alain Goriely, Jordan W. Raff

Research output: Contribution to journal › Article › peer-review

Abstract

Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome “maturation” requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process—peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.

Original language	English
Article number	e110891
Journal	EMBO Journal
Volume	41
Issue number	11
Early online date	3 May 2022
DOIs	https://doi.org/10.15252/embj.2022110891
Publication status	Published - 1 Jun 2022
Externally published	Yes

Keywords

cell cycle
centrosome
oscillator
PCM
PLK1

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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10.15252/embj.2022110891Licence: CC BY

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title = "Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly",

abstract = "Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome “maturation” requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process—peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.",

keywords = "cell cycle, centrosome, oscillator, PCM, PLK1",

author = "Wong, {Siu Shing} and Wilmott, {Zachary M.} and Saroj Saurya and Ines Alvarez-Rodrigo and Zhou, {Felix Y.} and Chau, {Kwai Yin} and Alain Goriely and Raff, {Jordan W.}",

note = "Funding Information: We are grateful to Stefano di Thalia (Duke University, USA) and Thomas Steinacker (Raff Lab) for communicating unpublished data, to Lisa Gartenmann for generating the Ubq‐NG‐Cnn line used in this study and to Alan Wainman for help with microscopy as part of the Micron Oxford Advanced Bioimaging Unit—partly funded by a Strategic Award from the Wellcome Trust (107457). We thank members of the Raff Laboratory for advice, discussion and for critically reading the manuscript. The research was funded by a Wellcome Trust Senior Investigator Award (215523) to JWR, an EPSRC award (EP/R020205/1) and a John Fell Fund Award to AG, and a CRUK Oxford Centre Prize DPhil Studentship (C5255/A23225), a Balliol Jason Hu Scholarship and a Clarendon Scholarship (to SSW). ",

year = "2022",

month = jun,

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doi = "10.15252/embj.2022110891",

language = "English",

volume = "41",

journal = "EMBO Journal",

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T1 - Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly

AU - Wong, Siu Shing

AU - Wilmott, Zachary M.

AU - Saurya, Saroj

AU - Alvarez-Rodrigo, Ines

AU - Zhou, Felix Y.

AU - Chau, Kwai Yin

AU - Goriely, Alain

AU - Raff, Jordan W.

N1 - Funding Information: We are grateful to Stefano di Thalia (Duke University, USA) and Thomas Steinacker (Raff Lab) for communicating unpublished data, to Lisa Gartenmann for generating the Ubq‐NG‐Cnn line used in this study and to Alan Wainman for help with microscopy as part of the Micron Oxford Advanced Bioimaging Unit—partly funded by a Strategic Award from the Wellcome Trust (107457). We thank members of the Raff Laboratory for advice, discussion and for critically reading the manuscript. The research was funded by a Wellcome Trust Senior Investigator Award (215523) to JWR, an EPSRC award (EP/R020205/1) and a John Fell Fund Award to AG, and a CRUK Oxford Centre Prize DPhil Studentship (C5255/A23225), a Balliol Jason Hu Scholarship and a Clarendon Scholarship (to SSW).

PY - 2022/6/1

Y1 - 2022/6/1

N2 - Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome “maturation” requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process—peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.

AB - Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome “maturation” requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process—peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.

KW - cell cycle

KW - centrosome

KW - oscillator

KW - PCM

KW - PLK1

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DO - 10.15252/embj.2022110891

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AN - SCOPUS:85129463331

VL - 41

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 11

M1 - e110891

ER -

Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly

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