A non-canonical mechanism for Crm1-export cargo complex assembly

Plants, fungi, and animals store their genetic material within the nucleus of each of their cells. This structure is surrounded by a double layer of membrane that prevents the contents of the nucleus from mixing with the contents of the rest of the cell (namely the cytoplasm). Exchange of material between the nucleus and cytoplasm occurs through pores embedded within the nuclear membrane. To travel through one of these pores, large molecules (also called cargos) require the assistance of so-called ‘transport receptors’ such as the Crm1 protein. This protein recognizes and binds to the part of a cargo molecule called a ‘nuclear export signal’, and the Crm1 protein also binds to another protein called RanGTP. Nuclear export signals bind weakly to Crm1, which in turn ensures that these cargos are easily released in the cytoplasm once transport is completed. However, this weak binding means that it has remained a mystery how Crm1 is able to efficiently transport cargos out of the nucleus to begin with. Now, Fischer et al. have analyzed how one cargo that contains a nuclear export signal, namely molecules called ribosome precursors, assembles with Crm1. The experiments identified another protein called Slx9 that shuttles rapidly between the inside and the outside of the nucleus. Fischer et al. observed that Slx9 binds directly to RanGTP and brings it together with the ribosome precursor cargo. When a complex of Slx9, RanGTP, and cargo is assembled, it further recruits Crm1 to the cargo. Thus, Slx9 acts as a scaffold to bring cargo into contact with Crm1 and RanGTP, and a tight complex is formed that enables the export of the cargo out of the nucleus. Yeast cells lacking Slx9 delay export of ribosome precursors out of the nucleus. These findings imply the existence of yet-unidentified proteins like Slx9 that help Crm1 to rapidly transport diverse cargos out from the nucleus and into the cytoplasm.