How does cargo get released inside the nucleus during nuclear import?

The process of cargo release inside the nucleus during nuclear import primarily involves the hydrolysis of Ran-GTP. In nuclear transport, cargo proteins are first bound by import receptors in the cytoplasm. These import receptors carry the cargo into the nucleus through nuclear pore complexes. Once inside the nucleus, the concentration of Ran-GTP is significantly higher than that of Ran-GDP.

Upon entering the nucleus, Ran-GTP binds to the import receptor. This interaction triggers a conformational change in the import receptor that causes it to release the bound cargo protein. The hydrolysis of Ran-GTP to Ran-GDP, which occurs soon after this binding, is critical because it reduces the affinity of the receptor for the cargo, allowing it to be released effectively.

In summary, cargo release occurs as a result of the binding of Ran-GTP to the import receptor inside the nucleus, and subsequently, the hydrolysis of Ran-GTP facilitates a change in receptor structure that leads to dissociation of the cargo. This mechanism is a key part of the regulated and selective process of nuclear import.