Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

Abstract

Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. 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 signaling 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 proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss 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.

• Authors: Lucas V Cairo, Christopher Ptak, Richard W Wozniak
• Journal: Nucleus (Austin, Tex.) (Nucleus) 2013 Sep-Oct Vol. 4 Issue 5 Pg. 367-73 ISSN: 1949-1042 [Electronic] United States
• PMID: 24076561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cell Cycle Proteins
• Receptors, Cytoplasmic and Nuclear

Topics

• Active Transport, Cell Nucleus
• Animals
• Cell Cycle Checkpoints
• Cell Cycle Proteins (metabolism)
• Cell Nucleus (metabolism)
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Spindle Apparatus (metabolism)