Nuclear transport

Nuclear transport refers to the mechanisms by which molecules move across the

Nuclear export roughly reverses the import process; in the nucleus, the exportin binds the cargo and Ran-GTP and diffuses through the pore to the cytoplasm, where the complex dissociates. Ran-GTP binds GAP and hydrolyzes GTP, and the resulting Ran-GDP complex is restored to the nucleus where it exchanges its bound ligand for GTP. Hence, whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo.[4]

A specialized mRNA exporter protein moves mature mRNA to the cytoplasm after post-transcriptional modification is complete. This translocation process is actively dependent on the Ran protein, although the specific mechanism is not yet well understood. Some particularly commonly transcribed genes are physically located near nuclear pores to facilitate the translocation process.^[5]

Export of tRNA is also dependent on the various modifications it undergoes, thus preventing export of improperly functioning tRNA. This quality control mechanism is important due to tRNA's central role in translation, where it is involved in adding amino acids to a growing peptide chain. The tRNA exporter in vertebrates is called exportin-t. Exportin-t binds directly to its tRNA cargo in the nucleus, a process promoted by the presence of RanGTP. Mutations that affect tRNA's structure inhibit its ability to bind to exportin-t, and consequentially, to be exported, providing the cell with another quality control step.^[6] As described above, once the complex has crossed the envelope it dissociates and releases the tRNA cargo into the cytosol.

Protein shuttling

Many proteins are known to have both NESs and NLSs and thus shuttle constantly between the nucleus and the cytosol. In certain cases one of these steps (i.e., nuclear import or nuclear export) is regulated, often by

Nuclear import limits the propagation of large proteins expressed in skeletal muscle fibers and possibly other syncytial tissues, maintaining localized gene expression in certain nuclei.^[7] Combining both NESs and NLSs promotes propagation of large proteins to more distant nuclei in muscle fibers.^[8]

Protein shuttling can be assessed using a heterokaryon fusion assay.^[9]

References