A possible mechanism for self coordination of bi-directional traffic across nuclear pores

TL;DR

This paper proposes a computer simulation-based model explaining how nuclear pores manage bidirectional traffic without active gating, revealing two distinct traffic modes influenced by cargo concentration and dissociation rates.

Contribution

It introduces a novel simulation approach showing spontaneous traffic mode switching in nuclear pores based on cargo dynamics, without requiring active gating mechanisms.

Findings

Traffic can exist in two modes: fluctuating and regulated.

High cargo concentration and slow dissociation lead to directional traffic.

Exit rate from the pore influences traffic behavior.

Abstract

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 bi-directional 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 analyzed under different conditions. We suggest that traffic can exist in two distinct modes, depending on 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 the other direction. The result is that overall-traffic-direction fluctuates rapidly and unsystematically between import and export. Remarkably, when cargo concentrations are high and dissociation 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.