Figure 1.
Mechanisms of protein nuclear import. Cargos targeted for nuclear import contain NLSs on their surface which interact with a number of distinct importin-α/β heterodimers or importin-β isoforms directly. These complexes are targeted to and translocated across the nuclear envelope through the NPC. Upon reaching the nucleus, RanGTP binds to importin-β, causing a conformational change that releases the bound cargo. The importins are then recycled to the cytoplasm as a RanGTP–Importin-β complex or, in the case of importin-α, by its export carrier CAS. The complex then dissociates in the cytoplasm after the hydrolysis of RanGTP, which is facilitated by RanGAP at the cytoplasmic face of the NPC. RanGDP is then imported to the nucleus by NTF2 and the guanine exchange factor RCC1 converts it to RanGTP.