Working model of the role of NPC motility in organizing chromosomes and mediating nucleoplasmic transport. (A) Nuclear organization in a wild-type cell. Chromosomes are constantly rearranged by NPC motility. This results in an even distribution of the NPCs. Import and export cargo diffuses through channels between the chromosomes. For sake of simplicity only export cargo is indicated. (B) Nuclear organization in a mutant defective in kinesin-1 and dynein. NPCs are no longer transported along microtubules. As a consequence they form clusters that concentrate the attached chromosomes at the cell periphery. This blocks diffusion channels between chromosomes, which in turn impairs nucleoplasmic transport. Note that the adapters between the motors and the NPC are not known (?).