The molecular mechanism of transport of macromolecules through nuclear pore complexes

Trafficking of macromolecules between nuclear and cytoplasmic compartments takes place through the nuclear pore complexes (NPCs) of the nuclear envelo pe. Nuclear trafficking involves a complex series of interactions between c argo, soluble transport factors (carriers) and nuclear pore proteins (nucle oporins) that are orchestrated by the Ras-family GTPase Ran. The primary ro le of Ran is probably to establish directionality and to sort molecules to be transported by controlling the interaction between carriers and cargoes, so that they bind in one compartment but dissociate in the other. Transloc ation of carriers and cargo-carrier complexes through NPCs requires interac tions between the carriers and nucleoporins that contain distinctive tandem sequence repeats based on cores rich in glycine and phenylalanine residues that are separated by hydrophilic linkers. Much recent work has focused on these interactions and, in particular. their specificity, regulation and f unction. Evidence is accumulating that carriers move through the NPC by dis tinct but overlapping routes using specific subsets of nucleoporins.