The nuclear pore complex (NPC) is a large protein assembly that controls the transport of macromolecules into and out of the nucleus. Among its constituents are the pore membrane nucleoporins (Poms), which are thought to be crucial for anchoring the NPC within the nuclear membrane. However, the mechanisms that govern the localisation of Poms to the nuclear pores are not fully understood. In this work (p. 305), Valérie Doye and colleagues now further characterise the factors that determine the targeting of yeast Pom33, which they have previously shown to be an integral membrane protein that dynamically associates with NPCs. They first employ an affinity purification assay to search for Pom33 interaction partners and identify Kap123, a member of the karyopherin family of nuclear transport receptors. Pom33 interacts with Kap123 through its C-terminal domain (CTD), which behaves as a nuclear localisation signal (NLS). However, loss of Kap123 binding did not have any effect on Pom33 localisation, indicating that other factors might be involved. Indeed, the authors show that the CTD of Pom33 also contains a pair of amphipathic α-helices with a high affinity for highly curved membranes, such as those found underneath the NPC structure. Only alteration of both Kap123 interaction and the α-helices impaired Pom33 targeting to the NPC, indicating that multiple mechanisms are required for proper NPC targeting of Pom33.

© 2015. Published by The Company of Biologists Ltd
2015