The importin β binding domain as a master regulator of nucleocytoplasmic transport

Specific and efficient recognition of import cargoes is essential to ensure nucleocytoplasmic transport. To this end, the prototypical karyopherin importin beta associates with import cargoes directly or, more commonly, through import adaptors, such as importin alpha and snurportin. Adaptor proteins bind the nuclear localization sequence (NLS) of import cargoes while recruiting importin beta via an N-terminal importin beta binding (IBB) domain. The use of adaptors greatly expands and amplifies the repertoire of cellular cargoes that importin beta can efficiently import into the cell nucleus and allows for fine regulation of nuclear import. Accordingly, the IBB domain is a dedicated NLS, unique to adaptor proteins that functions as a molecular liaison between importin beta and import cargoes. This review provides an overview of the molecular role played by the IBB domain in orchestrating nucleocytoplasmic transport. Recent work has determined that the IBB domain has specialized functions at every step of the import and export pathway. Unexpectedly, this stretch of similar to 40 amino acids plays an essential role in regulating processes such as formation of the import complex, docking and translocation through the nuclear pore complex (NPC), release of import cargoes into the cell nucleus and finally recycling of import adaptors and importin beta into the cytoplasm. Thus, the IBB domain is a master regulator of nucleocytoplasmic transport, whose complex molecular function is only recently beginning to emerge. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import. (C) 2010 Elsevier B.V. All rights reserved.