Karyopherin-mediated nucleocytoplasmic transport

Efficient and regulated nucleocytoplasmic trafficking of macromolecules to the correct subcellular compartment is critical for proper functions of the eukaryotic cell. The majority of the macromolecular traffic across the nuclear pores is mediated by the Karyopherin-beta (or Kap) family of nuclear transport receptors. Work over more than two decades has shed considerable light on how the different Kap family members bring their respective cargoes into the nucleus or the cytoplasm in efficient and highly regulated manners. In this Review, we overview the main features and established functions of Kap family members, describe how Kaps recognize their cargoes and discuss the different ways in which these Kap-cargo interactions can be regulated, highlighting new findings and open questions. We also describe current knowledge of the import and export of the components of three large gene expression machines - the core replisome, RNA polymerase II and the ribosome - pointing out the questions that persist about how such large macromolecular complexes are trafficked to serve their function in a designated subcellular location. The majority of macromolecules are transported across the nuclear membrane by the Karyopherin-beta (Kap) proteins, comprising importins, exportins and biportins. Unravelling mechanisms and regulation of Kap-cargo interactions is essential for understanding nuclear export and import of proteins and RNA and how this traffic impacts their physiological functions.

Automated summary

Efficient and regulated nucleocytoplasmic trafficking is crucial for the proper functions of eukaryotic cells. The Karyopherin-beta (Kap) family of nuclear transport receptors mediates the majority of macromolecular traffic across the nuclear pores. Understanding how Kap family members transport their cargoes into the nucleus or the cytoplasm and how these interactions are regulated is essential for understanding nuclear export and import of proteins and RNA and their physiological functions.