The Cep57-pericentrin module organizes PCM expansion and centriole engagement

Nature Communications
Koki WatanabeDaiju Kitagawa

Abstract

Centriole duplication occurs once per cell cycle to ensure robust formation of bipolar spindles and chromosome segregation. Each newly-formed daughter centriole remains connected to its mother centriole until late mitosis. The disengagement of the centriole pair is required for centriole duplication. However, the mechanisms underlying centriole engagement remain poorly understood. Here, we show that Cep57 is required for pericentriolar material (PCM) organization that regulates centriole engagement. Depletion of Cep57 causes PCM disorganization and precocious centriole disengagement during mitosis. The disengaged daughter centrioles acquire ectopic microtubule-organizing-center activity, which results in chromosome mis-segregation. Similar defects are observed in mosaic variegated aneuploidy syndrome patient cells with cep57 mutations. We also find that Cep57 binds to the well-conserved PACT domain of pericentrin. Microcephaly osteodysplastic primordial dwarfism disease pericentrin mutations impair the Cep57-pericentrin interaction and lead to PCM disorganization. Together, our work demonstrates that Cep57 provides a critical interface between the centriole core and PCM.

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Citations

May 12, 2019·Biology of Reproduction·Svetlana A Yatsenko, Aleksandar Rajkovic
Mar 15, 2020·Biology of the Cell·Véronique Marthiens, Renata Basto
Jul 17, 2020·Frontiers in Pediatrics·Masoud Dehghan TezerjaniMasoud Rahmanian
Sep 30, 2020·Cells·Rustem E Uzbekov, Tomer Avidor-Reiss
Jan 15, 2021·The Journal of Cell Biology·Takumi ChinenDaiju Kitagawa
Jan 19, 2021·Seminars in Cell & Developmental Biology·Swadhin Chandra Jana
Apr 12, 2020·Trends in Molecular Medicine·Andrea RemoMassimo Pancione
Dec 7, 2020·Current Opinion in Structural Biology·Cayetano Gonzalez
Nov 12, 2020·Current Opinion in Structural Biology·Kyung S LeeYan Zeng
Apr 11, 2021·Seminars in Cell & Developmental Biology·Alejandra Vasquez-Limeta, Jadranka Loncarek
May 14, 2021·The Journal of Cell Biology·Franz MeitingerJadranka Loncarek
Aug 27, 2021·Journal of Cardiovascular Development and Disease·Jakob SteinfeldtFelix B Engel
Jul 28, 2021·Annual Review of Cell and Developmental Biology·Sónia Gomes PereiraMónica Bettencourt-Dias

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Methods Mentioned

BETA
co-immunoprecipitation
co-IP
pull-down
two-hybrid
transfection
electrophoresis

Software Mentioned

Clustal Omega
Huygens essential SVI
Scientific Volume Imaging
Huygens
Mathematica
BLAST
Adobe Photoshop
ImageJ

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