A possible mechanism for self-coordination of bidirectional traffic across nuclear pores.
Nuclear pore complexes are constantly confronted by large fluxes of macromolecules and macromolecular complexes that need to get into and out of the nucleus. Such bidirectional traffic occurring in a narrow channel can easily lead to jamming. How then is passage between the nucleus and cytoplasm maintained under the varying conditions that arise during the lifetime of the cell? Here, we address this question using computer simulations in which the behaviour of the ensemble of transporting cargoes is analysed under different conditions. We suggest that traffic can exist in two distinct modes, depending on the concentration of cargoes and dissociation rates of the transport receptor-cargo complexes from the pores. In one mode, which prevails when dissociation is quick and cargo concentration is low, transport in either direction proceeds uninterrupted by transport in the other direction. The result is that the overall traffic direction fluctuates rapidly and unsystematically between import and export. Remarkably, when cargo concentrations are high and disassociation is slow, another mode takes over in which traffic proceeds in one direction for a certain extent of time, after which it flips direction for another period. The switch between this, more regulated, mode of transport and the other, quickly fluctuating state, does not require an active gating mechanism but rather occurs spontaneously through the dynamics of the transported particles themselves. The determining factor for the behaviour of traffic is found to be the exit rate from the pore channel, which is directly related to the activity of the Ran system that controls the loading and release of cargo in the appropriate cellular compartment.
Kapon
Ruti
R
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. ruti.kapon@weizmann.ac.il
Topchik
Alon
A
Mukamel
David
D
Reich
Ziv
Z
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism*; D008954:Models, Biological; D022022:Nuclear Pore / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013997:Time Factors
D018160:Receptors, Cytoplasmic and Nuclear