TMEM209/NPP-28 partitions PLK-1 between the nuclear envelope and nuclear interior during mitosis

Nuclear envelope breakdown (NEBD) requires disassembly of nuclear pore complexes (NPCs). Polo-like kinase 1 (Plk1/PLK-1) binds and phosphorylates NPCs to initiate NEBD. Plk1/PLK-1 also accumulates in the nucleus to regulate chromosome segregation. How Plk1/PLK-1 is spatially partitioned between NPCs and the nuclear interior is unknown. Here, we show NPP-28, the C. elegans homolog of transmembrane nucleoporin TMEM209, docks PLK-1 at the nuclear envelope and limits its nucleoplasmic accumulation. Deletion of npp-28 or mutation of PLK-1 docking sites reduces nuclear envelope-associated PLK-1 and increases its nucleoplasmic levels. Accordingly, npp-28 loss delays NEBD and promotes anaphase onset. PLK-1 phosphorylates NPP-28 in vitro, yet mutation of predicted PLK-1 phospo-sites in NPP-28 accelerates NEBD. Thus, unlike other nucleoporin substrates of PLK-1, NPP-28 phosphorylation prolongs NEBD. We also find context-dependent functional relationships between NPP-28 and other transmembrane nucleoporins. NPP-28 thus partitions PLK-1 between the nuclear envelope and nuclear interior to coordinate NEBD with anaphase onset.