On the asymmetric partitioning of nucleocytoplasmic transport - recent insights and open questions

Macromolecular cargoes are asymmetrically partitioned in the nucleus or cytoplasm by nucleocytoplasmic transport (NCT). At the center of this activity lies the nuclear pore complex (NPC), through which soluble factors circulate to orchestrate NCT. These include cargo-carrying importin and exportin receptors from the beta-karyopherin (Kap beta) family and the small GTPase Ran, which switches between guanosine triphosphate (GTP)- and guanosine diphosphate (GDP)-bound forms to regulate cargo delivery and compartmentalization. Ongoing efforts have shed considerable light on how these soluble factors traverse the NPC permeability barrier to sustain NCT. However, this does not explain how importins and exportins are partitioned in the cytoplasm and nucleus, respectively, nor how a steep RanGTP-RanGDP gradient is maintained across the nuclear envelope. In this Review, we peel away the multiple layers of control that regulate NCT and juxtapose unresolved features against known aspects of NPC function. Finally, we discuss how NPCs might function synergistically with Kap beta s, cargoes and Ran to establish the asymmetry of NCT.

Automated summary

This review examines the role of the nuclear pore complex in nucleocytoplasmic transport and discusses unresolved issues such as the partitioning of importin and exportin in the cytoplasm and nucleus, and the maintenance of the RanGTP-RanGDP gradient across the nuclear envelope.