PNET1 is an on-demand component of the nuclear pore complex gating cell proliferation rates

The nuclear pore complex (NPC) is a cornerstone of eukaryotic cell functionality, orchestrating the nucleocytoplasmic shuttling of macromolecules. Here, we report that PNET1, a transmembrane nucleoporin conserved between humans and plants, is a dynamic, adaptable NPC component, exclusively expressed in actively dividing cells. PNET1's selective integration is crucial for rapid cell growth in highly proliferative meristem and callus tissues in plants, as well as in lung cancer tissues in humans. We demonstrated that PNET1 acts as a pivotal tuner to coordinate mitotic disassembly and post-mitotic reassembly of the NPC during cell cycle. PNET1 hyper-phosphorylation disrupts its interaction with NPC scaffold, promoting NPC disintegration and nuclear membrane breakdown to trigger mitosis. Nascent, unphosphorylated PNET1 restores NPC interactions and recruits NPC scaffold for its reassembly during nuclear membrane rebuilding in daughter cells, continuing the cycle. Our findings reveal a previously uncharted mechanism that ensures rapid cell proliferation via exploiting an on-demand nucleoporin.