NIMA-related kinases (Neks) have known roles in cell-cycle regulation and ciliogenesis, but the recent finding that Neks are expressed in the nervous system suggests that they might also have a role in other cellular processes. On , Jeffrey Milbrandt and colleagues investigate the role of Nek3 in post-mitotic mouse neurons, and show that this kinase regulates neuronal morphology and polarity through effects on microtubules. Previously, the Thr475 residue was identified as a highly conserved phosphorylation site located in the PEST domain of Nek3; in this study, the authors show that the expression of Nek3 mutants lacking either the PEST domain or the Thr475 residue induces abnormal neuronal morphology, suggesting that Nek3 phosphorylation is essential for its normal function. Consistent with the known role of Neks in regulating microtubule dynamics, the authors show here that the expression of Nek3 mutants causes a decrease in the level of acetylated α-tubulin in neurons, although the overall α-tubulin network was not disrupted. Finally, they use inhibitors to show that the effects of the Nek3 mutants on α-tubulin are mediated by histone deacetylase 6 (HDAC6). The identity of the kinase that phosphorylates Nek3 at Thr475, and the nature of Nek3 downstream substrates, remain to be discovered.
