Importins and exportins in cellular differentiation

Abstract

The importin/exportin transport system provides the machinery involved in nucleocytoplasmic transport. Alterations of the levels of importins and exportins may play crucial roles in development, differentiation and transformation. Employing human leukaemia HL-60 cells, we and others have revealed the differentiation-associated changes in the protein and gene expression of these factors. The recent finding that a switch to the importin-alpha subtype triggers neural differentiation of embryonic stem cells underscores the importance of nucleocytoplasmic transport factors in cellular events. This review focuses on current research into the roles of importins and exportins in cell differentiation.

Fig 1

A basic model of importin/exportin-mediated nucleocytoplasmic transport of macromolecules. Importin-α (a) binds to the NLS within a protein cargo in the cytoplasm and forms a ternary complex with importin-β1 (β1) to enter into the nucleus. Some cargo molecules with the NLS can directly bind to importin-β1. In the nucleus, binding of RanGTP (the GTP-bound form of the small Ras family GTAse, Ran) to importin-β1 triggers the dissociation of the complex. For nuclear export, RanGTP stimulates binding of exportin (XPO) to an NES-containing cargo protein in the nucleus and the complex is exported to the cytoplasm, where hydrolysis of RanGTP to RanGDP results in complex disassembly.