Figure 10.

Meiosis I spindle formation is a result of Aurora A, Plk4, and Ran-GTP activity. Spindle assembly in the oocyte is a multistep process triggered by the cooperative activity of Plk4 (yellow) and Aurora A (red), which are essential to initiate microtubule growth at NEBD. Plk4 and Aurora A localize to MTOCs that are dispersed around condensed chromosomes. Aurora A activity is potentiated by Plk4, directly phosphorylating the kinase at five Ser/Thr residues including the T-loop activating site, but likely undergoing additional regulation by meiotic kinases and/or regulatory binding partners. Both Aurora A and Plk4 can have a distinct and shared set of substrates. We identify TACC3 as one potential downstream effector of Aurora A that localizes to MTOCs and whose phosphorylation is reduced upon Aurora A inhibition (see Fig. 4 C). Other pathways are likely acting at later stages of spindle assembly and are able to partially overcome the defects caused by inhibition of Aurora A and Plk4. One redundant pathway is Ran-GTP, which, by increasing levels of the allosteric Aurora A activator TPX2, is important for TACC3-mediated microtubule stabilization at the spindle poles.