A Mad that wears two hats: Mad1's control of nuclear trafficking

Abstract

In a recent issue of Molecular Cell, Cairo et al. (2013) report that the spindle checkpoint protein Mad1 shuttles between unattached kinetochores and nuclear pores. Mobile Mad1 inhibits the import receptor Kap121p, thus indirectly changing spindle dynamics. This adds nuclear transport control to the mitotic roles of Mad1.

Figure 1

Mad1-dependent sequestration in nucleoporin complexes during mitosis. A. In yeast, Mad1 associates with unattached kinetochores (KT), promoting Mad1's distinct roles in SAC signaling and in Ipl1p-dependent KTIP activation. Mad1 cycles to the NPC, where it interacts with Nup53 and causes re-configuration of nucleoporin interactions to arrest Kap121 transport of Glc7 and possibly other cargo proteins. B. During vertebrate mitosis, NPCs disassemble into a series of complexes containing multiple nucleoporin. As a speculative model, it is possible that kinetochore-activated Mad1 (Mad1*) could cause the re-arrangement of those complexes and the unmasking of high affinity Karyopherin binding sites (Nup*). The formation of stable karyopherin-cargo complexes in associate with these sites could alter the localization or function of karyopherin-bound cargo proteins (Cargo*).