Nuclear pores set the speed limit for mitosis

Abstract

The spindle assembly checkpoint prevents separation of sister chromatids until each kinetochore is attached to the mitotic spindle. Rodriguez-Bravo et al. report that the nuclear pore complex scaffolds spindle assembly checkpoint signaling in interphase, providing a store of inhibitory signals that limits the speed of the subsequent mitosis.

Figure 1. Nuclear pores impact the spindle assembly checkpoint

(i) The Mad1-Mad2 complex is anchored to the NPC via Tpr in interphase, where it catalyzes the activation of O-Mad2 to C-Mad2 as it traffics through the nuclear pore. Activated C-Mad2 then accumulates in APC/C inhibitory MCCs in the cytosol. (ii) The Mad1-Mad2 complex is anchored to unoccupied kinetochores during mitosis, generating more MCCs and preventing the metaphase-to-anaphase transition until all chromosomes are bioriented on the spindle. NPC, nuclear pore complex; NE, nuclear envelope; MCC, mitotic checkpoint complex.