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As cells enter mitosis, the two centrosomes separate and grow dramatically, each forming a nascent spindle pole that nucleates a radial array of microtubules. Centrosome growth (and associated microtubule nucleation surge), termed maturation, involves the recruitment of pericentriolar material components via an as-yet unknown mechanism. Here, we show that Cep192 binds Aurora A and Plk1, targets them to centrosomes in a pericentrin-dependent manner, and promotes sequential activation of both kinases via T-loop phosphorylation. The Cep192-bound Plk1 then phosphorylates Cep192 at several residues to generate the attachment sites for the γ-tubulin ring complex and, possibly, other pericentriolar material components, thus promoting their recruitment and subsequent microtubule nucleation. We further found that the Cep192-dependent Aurora A-Plk1 activity is essential for kinesin-5-mediated centrosome separation, bipolar spindle formation, and equal centrosome/centriole segregation into daughter cells. Thus, our study identifies a Cep192-organized signaling cascade that underlies both centrosome maturation and bipolar spindle assembly.
Al-Bassam,
Regulation of microtubule dynamics by TOG-domain proteins XMAP215/Dis1 and CLASP.
2011, Pubmed,
Xenbase
Al-Bassam,
Regulation of microtubule dynamics by TOG-domain proteins XMAP215/Dis1 and CLASP.
2011,
Pubmed
,
Xenbase
Archambault,
Polo-like kinases: conservation and divergence in their functions and regulation.
2009,
Pubmed
Azimzadeh,
Centrosome loss in the evolution of planarians.
2012,
Pubmed
Berdnik,
Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis.
2002,
Pubmed
,
Xenbase
Bettencourt-Dias,
Centrosome biogenesis and function: centrosomics brings new understanding.
2007,
Pubmed
Cheeseman,
Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p.
2002,
Pubmed
Conduit,
The centrosome-specific phosphorylation of Cnn by Polo/Plk1 drives Cnn scaffold assembly and centrosome maturation.
2014,
Pubmed
Decker,
Limiting amounts of centrosome material set centrosome size in C. elegans embryos.
2011,
Pubmed
Dix,
Drosophila Spd-2 recruits PCM to the sperm centriole, but is dispensable for centriole duplication.
2007,
Pubmed
Elia,
Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates.
2003,
Pubmed
Eyers,
A novel mechanism for activation of the protein kinase Aurora A.
2003,
Pubmed
,
Xenbase
Fu,
Structured illumination of the interface between centriole and peri-centriolar material.
2012,
Pubmed
Giansanti,
Drosophila SPD-2 is an essential centriole component required for PCM recruitment and astral-microtubule nucleation.
2008,
Pubmed
Gomez-Ferreria,
Human Cep192 is required for mitotic centrosome and spindle assembly.
2007,
Pubmed
Gomez-Ferreria,
Novel NEDD1 phosphorylation sites regulate γ-tubulin binding and mitotic spindle assembly.
2012,
Pubmed
Gomez-Ferreria,
Cep192 and the generation of the mitotic spindle.
2008,
Pubmed
Hannak,
Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans.
2001,
Pubmed
Haren,
Plk1-dependent recruitment of gamma-tubulin complexes to mitotic centrosomes involves multiple PCM components.
2009,
Pubmed
Haren,
NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly.
2006,
Pubmed
Joukov,
Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle assembly by engaging in organelle-specific Aurora A activation.
2010,
Pubmed
,
Xenbase
Joukov,
Aurora kinases and spindle assembly: variations on a common theme?
2011,
Pubmed
Kemp,
Centrosome maturation and duplication in C. elegans require the coiled-coil protein SPD-2.
2004,
Pubmed
,
Xenbase
Kim,
Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152.
2013,
Pubmed
Kollman,
Microtubule nucleation by γ-tubulin complexes.
2011,
Pubmed
Lane,
Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.
1996,
Pubmed
Lawo,
Subdiffraction imaging of centrosomes reveals higher-order organizational features of pericentriolar material.
2012,
Pubmed
Lee,
PLK1 phosphorylation of pericentrin initiates centrosome maturation at the onset of mitosis.
2011,
Pubmed
Loncarek,
Centriole reduplication during prolonged interphase requires procentriole maturation governed by Plk1.
2010,
Pubmed
Lüders,
GCP-WD is a gamma-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation.
2006,
Pubmed
Macůrek,
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
2008,
Pubmed
Mahen,
Pattern formation in centrosome assembly.
2012,
Pubmed
Mardin,
Breaking the ties that bind: new advances in centrosome biology.
2012,
Pubmed
,
Xenbase
Mennella,
Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization.
2012,
Pubmed
Mennella,
Amorphous no more: subdiffraction view of the pericentriolar material architecture.
2014,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nigg,
Centrioles, centrosomes, and cilia in health and disease.
2009,
Pubmed
Nikonova,
Aurora A kinase (AURKA) in normal and pathological cell division.
2013,
Pubmed
Park,
Polo-box domain: a versatile mediator of polo-like kinase function.
2010,
Pubmed
Pelletier,
The Caenorhabditis elegans centrosomal protein SPD-2 is required for both pericentriolar material recruitment and centriole duplication.
2004,
Pubmed
Pinyol,
The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function.
2013,
Pubmed
,
Xenbase
Seki,
Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry.
2008,
Pubmed
,
Xenbase
Sir,
Loss of centrioles causes chromosomal instability in vertebrate somatic cells.
2013,
Pubmed
Sonnen,
Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication.
2013,
Pubmed
Sonnen,
3D-structured illumination microscopy provides novel insight into architecture of human centrosomes.
2012,
Pubmed
Tsai,
Aurora A kinase-coated beads function as microtubule-organizing centers and enhance RanGTP-induced spindle assembly.
2005,
Pubmed
,
Xenbase
Verstraeten,
Protein farnesylation inhibitors cause donut-shaped cell nuclei attributable to a centrosome separation defect.
2011,
Pubmed
Wang,
The conversion of centrioles to centrosomes: essential coupling of duplication with segregation.
2011,
Pubmed
Zhang,
Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome.
2009,
Pubmed
Zhu,
The mammalian SPD-2 ortholog Cep192 regulates centrosome biogenesis.
2008,
Pubmed
