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In Ran mutants, nups get stuck in vesicles (*) rather than assembling into NPCs (arrowheads).

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 that accumulated throughout the cytoplasm.

Thus, RanGTP may be involved in the fusion of vesicles at the nuclear envelope. This cytoplasmic Ran function contrasts with the current dogma that GTP-bound Ran is primarily nuclear. The authors hypothesize that a yet unidentified GEF could produce RanGTP at the cytoplasmic side of the NE. Alternatively, the nuclear RanGEF Prp20 (mutations in which were isolated in this NPC screen) may have a small cytoplasmic pool that has so far gone undetected.

At the other end of the NPC lifecycle, a report on page 1055 by Lénárt et al. describes NPC disassembly as the initiating step in the breakdown of the NE preceding mitosis. The group identified two distinct phases of NE breakdown in starfish oocytes based on permeabilization of the nucleus. During the first phase, the gradual release of nups from the NPC led to a small increase in NPC permeability. In the second phase, a wave of permeabilization spread rapidly from an epicenter-like origin, and gaps appeared in the NE, possibly caused by removal of entire NPCs. Even at this point, the NE was still attached to the polymerized lamina along its inner membrane, indicating that disassembly of this network of intermediate filaments is a late step in NE breakdown. ▪