Figure 1.

Asymmetry of the Tem1 GTPase at SPBs is broken upon spindle misalignment. (A) When cells align properly their mitotic spindles along the mother-to-bud polarity axis the Tem1 GTPase localizes preferentially to the bud-directed SPB and triggers the Mitotic Exit Network (MEN) kinase cascade (Cdc15, Dbf2-Mob1) that leads to the activation of Cdc14 phosphatase and mitotic exit. Two separated compartments for inhibition and activation of the MEN are defined in the mother cell and in the bud by Kin4 and Lte1, respectively, and depicted in red and green. (B) Upon spindle misalignment Tem1 localizes symmetrically on both SPBs and the Spindle Position Checkpoint (SPOC) inhibits Tem1 through the GTPase-Activating Protein (GAP) complex Bub2-Bfa1, thereby restraining the MEN until the spindle repositions correctly. The GAP is in turn kept active by the kinase Kin4, which counteracts the inhibitory phosphorylation of the GAP by the Polo kinase Cdc5.