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Register a new userA possible mechanism for self coordination of bi-directional traffic across nuclear pores
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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.
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Several important biological processes are initiated by the binding of a protein to a specific site on the DNA. The strategy adopted by a protein, called transcription factor (TF), for searching its specific binding site on the DNA has been investigated over several decades. In recent times the effects obstacles, like DNA-binding proteins, on the search by TF has begun to receive attention. RNA polymerase (RNAP) motors collectively move along a segment of the DNA during a genomic process called transcription. This RNAP traffic is bound to affect the diffusive scanning of the same segment of the DNA by a TF searching for its binding site. Motivated by this phenomenon, here we develop a kinetic model where a `particle, that represents a TF, searches for a specific site on a one-dimensional lattice. On the same lattice another species of particles, each representing a RNAP, hop from left to right exactly as in a totally asymmetric simple exclusion process (TASEP) which forbids simultaneous occupation of any site by more than one particle, irrespective of their identities. Although the TF is allowed to attach to or detach from any lattice site, the RNAPs can attach only to the first site at the left edge and detach from only the last site on the right edge of the lattice. We formulate the search as a {it first-passage} process; the time taken to reach the target site {it for the first time}, starting from a well defined initial state, is the search time. By approximate analytical calculations and Monte Carlo (MC) computer simulations, we calculate the mean search time. We show that RNAP traffic rectifies the diffusive motion of TF to that of a Brownian ratchet, and the mean time of successful search can be even shorter than that required in the absence of RNAP traffic. Moreover, we show that there is an optimal rate of detachment that corresponds to the shortest mean search time.
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