Schematic representation of the nuclear import cycle. The cargo (red) with a NLS binds impα and then impβ binds to impα forming a trimeric complex in the presence of RanGDP. The trimeric complex goes across nuclear pores and reaches the inner nuclear region. Here high levels of RanGTP induce a conformational change in impβ, which dissociates from the cargo and shuttles back to the cytoplasm. Impα binds to CAS in the nucleus and forms a complex with RanGTP. Such complex is exported from the nucleus and dissociates in the cytoplasm upon conversion of RanGTP into RanGDP. RanGDP is imported into the nucleus by NTF2. In the nucleus, RanGDP is rapidly converted into RanGTP by RCC1. At the cytoplasmic face of the nuclear pore, RanGTP in converted to RanGDP by RanGAP, RanBP1 and RanBP2. Thus a gradient of RanGTP across the nuclear envelope is maintained, which gives directionality to the import/export process.