Building and breaking the NPC

Astudy of nuclear pore complex (NPC) assembly is revealing Ran to be a ubiquitous regulator of nuclear physiology. RanGTP gradients are essential for nuclear trafficking, spindle assembly during mitosis, and reformation of the nuclear envelope (NE) after mitosis. Now, on page 1041, Ryan et al. implicate Ran in yet another nuclear function—NPC assembly.

In a screen for budding yeast NPC mutants, the authors identified several temperature-sensitive mutations in the Ran pathway, including mutations in a Ran guanine nucleotide exchange factor, a Ran GTPase activating protein, a nuclear importer of RanGDP, and the GTPase itself. Although preexisting NPCs were stable in the mutants, newly synthesized nucleoporin proteins (nups) were mislocalized at the restrictive temperature. Rather than localizing to the NE, several peripheral and integral membrane nups were found in vesicles...