Nuclear Localization Signals and Import

Proteins imported from the cytosol to the nucleus contain short stretches of amino acid sequences called nuclear localization signals or NLS.

Importins, specialized nuclear import receptors, recognize the NLS of cargo proteins and transport them to the nucleus through the nuclear pore complexes or NPCs.

Importins are present in the cytosol as soluble dimers of an alpha and a beta subunit. Importin alpha binds the NLS of a cargo protein to form a cargo-receptor complex.

Importin beta binds cytoplasmic fibrils extending from the NPC and docks the cargo-receptor complex onto the channel's opening.

The inner channel of the NPC is lined with phenylalanine-glycine or FG-rich repeats that form a gel-like selective barrier.

As the cargo-receptor complex moves through the channel, the beta subunit makes multiple weak contacts with the FG repeats and hops across the channel, breaking the interactions between the FG repeats and dissolving the gel-like barrier. Through such repeated contacts and dissolution, the cargo-receptor complex travels inside the nucleus.

Within the nucleus, a GTP-bound protein called Ran binds importin beta and induces a conformational change in the receptor to release the cargo protein.

The importin-Ran-GTP complex is then transported back to the cytosol, where GTP is hydrolyzed, releasing the importins for another round of cargo import.