37 research outputs found
Nucleocytoplasmic transport: a thermodynamic mechanism
The nuclear pore supports molecular communication between cytoplasm and
nucleus in eukaryotic cells. Selective transport of proteins is mediated by
soluble receptors, whose regulation by the small GTPase Ran leads to cargo
accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear
export. We consider the operation of this transport system by a combined
analytical and experimental approach. Provocative predictions of a simple model
were tested using cell-free nuclei reconstituted in Xenopus egg extract, a
system well suited to quantitative studies. We found that accumulation capacity
is limited, so that introduction of one import cargo leads to egress of
another. Clearly, the pore per se does not determine transport directionality.
Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic
concentration in steady-state. The model shows that this ratio should in fact
be independent of the receptor-cargo affinity, though kinetics may be strongly
influenced. Numerical conservation of the system components highlights a
conflict between the observations and the popular concept of transport cycles.
We suggest that chemical partitioning provides a framework to understand the
capacity to generate concentration gradients by equilibration of the
receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures,
plus Supplementary Material include