Figure 9.

A model illustrating Nek2 dynamics in the cell. Immuno-EM studies suggest that Nek2 (red), together with its substrate C-Nap1 (orange), preferentially localize to the proximal ends of the two centrioles (blue cylinders), whereas neither protein requires an intact microtubule cytoskeleton to maintain their centrosomal localization (Fry et al., 1998b). However, this current study reveals that a number of mechanisms are involved in regulating Nek2 trafficking to the centrosome. (1) FRAP and FLIP indicate that Nek2 can load on and off the centrosome independently of microtubules. (2) Time-lapse imaging and FRAP studies suggest a possible contribution of microtubules to long-range transport of Nek2. (3) Partial colocalization of Nek2 with PCM-1 highlights a possible role for PCM-1 in delivery of Nek2 to the centrosome along microtubules. (4) Alternatively, PCM-1 may have a chaperone function in facilitating assembly of protein complexes, in this case Nek2 and C-Nap1, before transport to the centrosome. (5) Proteasomal degradation of Nek2A is essential to allow turnover of Nek2 molecules at the centrosome. Together, these processes ensure the correct abundance of Nek2 kinase at the centrosome through the cell cycle.