Active nuclear transport in living cells: dynamics and steady-state profiles of cargo concentrations

The transport of cargo into and out of the nucleus is crucial for the functioning of all eukaryotes cells. Although the migration of ions and small molecules can occur diffusively, the nuclear transport of larger macromolecules generally requires an active process. Large protein channels known as nuclear pores embedded into nuclear envelope regulate the passage of many proteins and RNA molecules. However, their movement through nuclear pores does not require energy input, the nuclear transport being powered in large part by the free energy transduction from the Ran cycle. At the energetic cost of guanosine triphosphate hydrolysis, the system of nuclear pores and corresponding transport receptors is able to generate steep concentration gradients across the nuclear envelope, thereby controlling the flux and directionality of nucleocytoplasmic transport. Here, a physical model of this mechanism is described that allows us to determine the temporal and spatial distributions of transport receptors and cargo proteins within the nucleus, and their role in the regulation of other cellular processes such as chromatin remodeling and transcription is discussed.