There is a bidirectional flow of proteins through the nucleus. tRNAs and mRNAs are synthesized, for example, in the nucleus and transported out to the cytosol. Vice versa, proteins like histones, DNA and RNA polymerases, gene regulatory proteins, and RNA processing proteins are imported into the nucleus from the cytosol.
The nuclear envelope encloses the DNA of a eucaryotic cell. The envelope consists of an inner nuclear membrane that contains specific proteins that act as binding sites for chromatin and for the protein meshwork of the nuclear lamina that provides structural support for the nuclear envelope. The inner membrane is surrounded by an outer nuclear membrane which is continuous with the membrane of the .endoplasmic reticulum. The envelope consists of two membranes that are penetrated by nuclear pores.
Each nuclear pore contains one or more aqueous channels through which small water soluble molecules can passively diffuse. Large molecules (above 17K daltons) are generally unable to diffuse the channels (which are about 9nm wide). Thus large molecules like ribosomal subunits are unable to be exported and molecules like polymerases are unable to be imported into the nucleus using simple diffusion. Instead, such molecules must rely upon specific receptor proteins that transport them through nuclear pore complexes. A single pore complex can conduct traffic of proteins which move both into and out of the nucleus. Not all types of proteins are, however, imported and exported into the nucleus. The process is a selective one which is controlled by either signal sequences or patches on the proteins which are either imported or exported.
Localization: Nuclear localization signals (NLSs) which are rich in positively charged amino acids like lysine and arginine are present only on proteins being imported into the nucleus. Such NLS are recognized by nuclear import receptors
Nuclear export signals which bind to their complementary nuclear export receptors determine which proteins are exported out of the nucleus.
In many cases, transport of nuclear proteins depends on the regulation of nuclear localization and export signals which are turned on or off, typically by phosphorylation.
Both the import and export of proteins through the nuclear pore complex requires energy which is provided by the hydrolysis of GTP by the GTPase Ran which can exist in 2 conformational states depending on whether GDP or GTP is bound. Conversion between the 2 states is provided by a cytosolic GTPase-activating protein (GAP) that triggers GTP hydrolysis and a nuclear guanine exchange factor (GEF) that promotes the exchange of GDP for GTP.
In nuclear import, the Ran-GDP and the protein with its nuclear localization signal come together with the nuclear import receptor, the import receptors then move with their bound cargo into the nuclear side of the pore complex where Ran-GTP binding causes the the import receptors to release their cargo. The now empty import receptor with Ran-GTP bound is transported back through the pore complex to the cytosol where Ran-GTP is converted back to Ran-GDP to complete the cycle. Nuclear export occurs by a similar mechanism exept that Ran-GTP in the nucleus promotes cargo binding to the export receptor and the export receptor releases both its cargo and Ran-GDP in the cytosol where it is hydrolyzed by Ran-GAP.
The transport of nuclear proteins through nuclear pore complexes is different from the transport of proteins across membranes of other organelles because it occurs through large aqueous pores rather than through a protein transporter in one or more lipid bilayers. Because of this, proteins can usually be transported from a pore complex in their fully folded conformation. Moreover, Nuclear translocation signals are not cleaved off after transport into or out of the nucleus. This is not the case with other membrane bound organelles where the signal sequence is often removed after protein translocation.