Dual personality of Mad1

Abstract

n uclear transport is a dynamic process that can be modulated in response to changes in cellular physi-ology. we recently reported that the transport activity of yeast nuclear pore complexes (nPcs) is altered in response to kinetochore-microtubule (Kt-mt) interaction defects. specifically, Kt detachment from mts activates a signal-ing pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. this loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear pro-teins. a key regulator of this process is the spindle assembly checkpoint pro-tein mad1p. in response to unattached Kts, mad1p dynamically cycles between nPcs and Kts. this cycling appears to induce nPc molecular rearrange-ments that prevent the nuclear import of Kap121p-cargo complexes. here, we dis-cuss the underlying mechanisms and the physiological relevance of mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.