Wee1 is a well-characterised cell-cycle checkpoint kinase that regulates mitotic entry in dividing cells. On page , Andreas Püschel and colleagues uncover a novel effect of Wee1 on cell polarity in post-mitotic neurons that is regulated by the kinases SadA and SadB (SadA/B). They show that Wee1 is expressed and has a functional role early during the development of hippocampal neurons when cells have several undifferentiated neurites, but that its expression declines later as the cells become polarised and form a single axon. If high Wee1 expression is maintained during later stages of differentiation, cell polarity is disrupted: instead of forming a single axon, developing neurons form multiple neurites that are positive for axonal markers and in some cases also for dendritic markers. But how is Wee1 expression regulated? In contrast to Wee1, the expression of SadA/B (which are known to be involved in axon formation) increases during later stages of neuronal development. SadA physically interacts with Wee1 and mediates an inhibitory phosphorylation at Ser642, which is necessary for the decrease in Wee1 expression. Accordingly, developing neurons from Sada−/−Sadb−/− mouse embryos continue to express Wee1 and are subsequently abnormal. Therefore, the authors conclude, SadA/B regulate Wee1 activity and expression in developing neurons, which thereby determines proper neuronal cell polarity.
