Figure 12.

Mechanism of nucleocytoplasmic transport through NPCs. Importins (Kapβ1) identify and shuttle NLS-cargo from the cytoplasm into the nucleus. The Kapβ1–cargo complex is disassembled in the nucleus by RanGTP, and is thought to return to the cytosol with Kapβ1. NES-cargo requires both RanGTP and exportin for export through NPCs. RanGAP triggers the hydrolysis of RanGTP to RanGDP in the cytosol, which releases Kaps and cargoes. RanGDP is imported into the nucleus by NTF2, where it is recharged into RanGTP by RanGEF. In the absence of Kaps, neither specific nor large nonspecific cargoes can access the NPC.