When protein sorting occurs, they are imported into different places via one of the following three ways:

1- Transport through nuclear pores: Nuclear pores are large complex structures in the nuclear envelope (double-membrane) that regulate movement of macromolecules (proteins and nucleic acids) in and out of the nucleus.

The nuclear envelope has many nuclear pores termed nuclear pore complex (NPC).

In the nucleoplasmic face of the NPC, a nuclear ring supports eight basket filaments joined by the terminal ring forming a structure called the nuclear basket. In the cytoplasmic face, the NPC’s cytoplasmic ring supports eight cytoplasmic filaments. In the center of the NPC, there are the central plug or transporter (protein) and spoke which connect the two ring subunits together.

This complex provides the nucleus with the ability to selectively allow entry and exit of molecules. Ions, metabolites, and small proteins can pass freely and nonselectively between the nucleus and the cytosol.

Large molecules, however, and macromolecular complexes carry sorting signals called nuclear localization signals (NLS) to which a nuclear import receptor protein (NIRP) will bind and direct through the pore. The NIRP are also called nuclear transport receptors (NTR) and leads the proteins (synthesized in the cytoplasm but required for the nucleus) into the NPC,

The NIR attaches to the NLS of the protein that wants to enter the nucleus, forming a NIR-protein complex, and delivers it in through the NPC.

Once inside, one of the proteins of the NPC is an enzyme named Ran-GTPase which functions to add the protein complex Ran-GTP to the NIR-protein complex and causes conformational changes in the latter’s polypeptide chain leading to the dissociation of the NIR from the protein intended for the nucleus. Ran-GTP is a complex of Ran protein attached to guanosine triphosphate (a nucleoside).

The NIR-Ran-GTP complex formed, then, is powered by GTP hydrolysis to GDP (guanosine diphosphate– di meaning two, as in only two phosphate groups remain attached to the guanosine nucleoside molecule) and exit the nucleus through the NPC. The Ran-GTP is thus converted to Ran-GDP which, once the NIR-Ran-GDP complex exits the nucleus, will dissociate from the NIR.

Nuclear export works similar to nuclear import, but in reverse and proteins contain a nuclear-export signal (NES).