The NIMA-family Kinase, Nek1 Affects the Stability of Centrosomes and Ciliogenesis

Background: Mutations in Nek1 (NIMA-Related Kinase 1) are causal in the murine models ofpolycystic kidney disease kat and kat2J. The Neks are known as cell cycle kinases, but recent workin protists has revealed that in addition to roles in the regulation of cell cycle progression, someNeks also regulate cilia. In most cells, cilia are disassembled prior to mitosis and are regeneratedafter cytokinesis. We propose that Neks participate in the coordination of ciliogenesis with cellcycle progression. Mammalian Nek1 is a candidate for this activity because renal cysts form inresponse to dysfunctional ciliary signalling.Results: Here we report that over-expression of full-length mNek1 inhibited ciliogenesis withoutdisrupting centrosomes in the murine renal epithelial cell line IMCD3. In contrast, over-expressionof the kinase domain with its associated basic region, but without the acidic domain, caused loss ofcentrosomes. As expected, these cells also failed to grow cilia. Both defective ciliogenesis inresponse to too much mNek1 and disassembly of centrosomes in response to expression of thekinase lacking the presumptive regulatory domain was abrogated by kinase-inactivating mutationsor by removal of the coiled-coil domain. We observed that kinase-inactive, C-terminal truncationsof mNek1 retaining the coiled-coil domain localized to the cilium, and we define a ciliary targetingregion within the coiled-coil domain.Conclusion: Based on our data, we propose that Nek1 plays a role in centrosome integrity,affecting both ciliogenesis and centrosome stability