Polo kinases are an evolutionarily conserved subfamily of Ser/Thr protein kinases that play pivotal roles in cellular proliferation. Outer Dense Fiber 2 (ODF2) was initially identified as a major component of sperm tail cytoskeleton, and was later suggested to be a centrosomal scaffold important for the recruitment of various proteins to somatic centrosomes. Here, we showed that a splicing variant of hODF2 called hCenexin1, but not hODF2, efficiently localized to somatic centrosomes via a splice-generated C-terminal extension and recruited a mitotic polo-like kinase 1 (Plk1) through a Cdc2-dependent phospho-S796 motif within the extension. The S796-dependent hCenexin1-Plk1 interaction and Plk1 activity were critical for the recruitment of pericentrin and gamma-tubulin, generation of microtubule organizing centers, and formation of proper bipolar spindles. Early in the cell cycle, hCenexin1, but not hODF2, also contributed to normal ninein recruitment and primary cilia formation but independently of Plk1 binding. These findings provide an unparalleled example of how a splice-generated C-terminal extension of a sperm tail-associating protein can mediate unanticipated phospho-dependent and independent centrosomal events at distinct stages of the somatic cell cycle.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010680-04
Application #
7733148
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2008
Total Cost
$310,192
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code