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MBC in Press, published online ahead of print January 19, 2005
Mol. Biol. Cell 10.1091/mbc.E04-08-0688

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Submitted on August 11, 2004
Revised on December 3, 2004
Accepted on January 6, 2005

Dynamic Recruitment of Nek2 Kinase to the Centrosome Involves Microtubules, PCM-1 and Localized Proteasomal Degradation

Rebecca S. Hames,* Renarta E. Crookes,*{dagger} Kees R. Straatman,{ddagger} Andreas Merdes,{sect} Michelle J. Hayes,* Alison J. Faragher,*|| and Andrew M. Fry*¶

Departments of *Biochemistry and {ddagger}Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom; {sect}Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom

Monitoring Editor: Tim Stearns

Centrosomes undergo dramatic changes in composition and activity during cell cycle progression. Yet mechanisms involved in recruiting centrosomal proteins are poorly understood. Nek2 is a cell cycle-regulated protein kinase required for regulation of centrosome structure at the G2/M transition. Here, we have addressed the processes involved in trafficking of Nek2 to the centrosome of human adult cells. We find that Nek2 exists in small, highly dynamic cytoplasmic particles that move to and from the centrosome. Many of these particles align along microtubules and a motif was identified in the Nek2 C-terminal noncatalytic domain that allows both microtubule binding and centrosome localization. FRAP experiments reveal that 70% of centrosomal Nek2 is rapidly turned over (t1/2~3 s). Microtubules facilitate Nek2 trafficking to the centrosome but only over long distances. Cytoplasmic Nek2 particles colocalize in part with PCM-1 containing centriolar satellites and depletion of PCM-1 interferes with centrosomal recruitment of Nek2 and its substrate C-Nap1. Finally, we show that proteasomal degradation is necessary to allow rapid recruitment of new Nek2 molecules to the centrosome. Together, these data highlight multiple processes involved in regulating the abundance of Nek2 kinase at the centrosome including microtubule binding, the centriolar satellite component PCM-1, and localized protein degradation.

Present addresses: {dagger}Department of Cytogenetics, Sheffield Children’s Hospital, Sheffield S10 2TH, United Kingdom; ||MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicester LE1 7RH, United Kingdom.

Corresponding author. E-mail: amf5{at}le.ac.uk






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