A transporter is required for localization of a nucleoporin (white).

In examining how the nuclear pore complex (NPC) is assembled, Lusk et al., reporting on page 267, have identified a series of interactions that could help explain both the assembly and the operation of these important structures.

NPCs are built with nucleoporins and then used to traffic karyopherins, proteins that escort molecular cargoes through the nuclear pore. Most nucleoporins bind to multiple karyopherins, but the yeast nucleoporin Nup53p is an exception, interacting only with the karyopherin Kap121p. Taking advantage of this, the authors determined that Kap121p is required for the proper targeting and assembly of Nup53p into the nuclear pore. The data suggest that in addition to binding Nup53p at the pore during translocation, Kap121p can bind to Nup53p that is in the cytoplasm to transport it to the nuclear membrane. Since similar interactions between other karyopherins and nucleoporins could also occur, this may be a general mechanism of nuclear pore assembly.

The authors propose that, once at the pore, Nup53p gets pulled away from its Kap121p escort by competitive binding to the nucleoporin Nup170p. In addition to explaining one aspect of assembly, the model suggests a mechanism for releasing karyopherins from nucleoporins. Competition for nucleoporin binding between a karyopherin and another nucleoporin could allow the now freed karyopherin and its cargo to progress to another nucleoporin on their way into or out of the nucleus. ▪