The Mechanism of Nucleocytoplasmic Transport through the Nuclear Pore Complex

Unlike their prokaryotic ancestors, eukaryotic cells contain numerous membrane-bound organelles that compartmentalize various specialized processes. This evolutionary advancement enabled tighter regulation of cellular functions but meant that cells needed to develop channels to transport proteins, ions, and other substances specifically across their internal and external membranes. Of all of the transport channels in a cell, one stands out from all of the others in terms of the range and size of cargoes that pass through it. This is the NPC, which mediates all transport across the nuclear envelope (NE) (the double-membraned layer that separates the nuclear genetic material from the cytoplasm). Transport through the NPC is rapid and bidirectional, with a large set of diverse cargoes crossing between the nucleus and cytoplasm. Cargoes such as transcription factors, ribosomal proteins, and viral nucleic acids enter the nucleus, whereas, messenger ribonucleoproteins (mRNPs), transfer RNAs (tRNAs), and ribosomal subunits exit. Despite the wide range of molecules that must pass through the NPC, nucleocytoplasmic transport is incredibly selective. Transport can also occur very quickly, up to the order of thousands of events per NPC per second Yet the structure of the NPC, discussed below, has been found to be surprisingly simple. How this simple structure might mediate this rapid yet selective transport of such a variety of cargoes remains the main question in the field and is the major topic of this chapter.