Nek7 kinase accelerates microtubule dynamic instability

Abstract

The NIMA-related kinases (NRK or Nek) are emerging as conserved and crucial regulators of mitosis and cilia formation. The microtubule (MT) network has long been suspected as a major target of the Neks. However, the underlying mechanism remains unclear. Using the PlusTipTracker software, recently developed by the Danuser group, we followed the consequences of alterations in Nek7 levels on MT dynamic instability. siRNA-mediated downregulation of Nek7 in HeLa cells resulted in lower speeds of MT growth and catastrophe, reduction of the relative time spent in catastrophe, and considerably lowered the overall MT dynamicity. Co-expression of Nek7 with the siRNA treatment rescued the MT phenotypes, while ectopic overexpression of Nek7 yielded inverse characteristics compared to Nek7 downregulation. MT dynamics in mouse embryonic fibroblasts derived from targeted null mutants for Nek7 recapitulated the siRNA downregulation phenotypes. Precise MT dynamic instability is critical for accurate shaping of the mitotic spindle and for cilium formation, and higher MT dynamicity is associated with tumorigenicity. Thus, our results can supply a mechanistic explanation for Nek involvement in these processes.