Regulation of mitosis in time and space is critical for proper cell division. We conducted an RNA interference–based modifier screen to identify novel regulators of mitosis in Caenorhabditis elegans embryos. Of particular interest, this screen revealed that the Nup205 nucleoporin NPP-3 can negatively modulate the timing of mitotic onset. Furthermore, we discovered that NPP-3 and nucleoporins that are associated with it are lost from the nuclear envelope (NE) in the vicinity of centrosomes at the onset of mitosis. We demonstrate that centrosomes are both necessary and sufficient for NPP-3 local loss, which also requires the activity of the Aurora-A kinase AIR-1. Our findings taken together support a model in which centrosomes and AIR-1 promote timely onset of mitosis by locally removing NPP-3 and associated nucleoporins from the NE.
Model for the role of centrosomes and AIR-1 in promoting NPP-3 local loss and timely mitotic entry in C. elegans embryos. Green circle: AIR-1 at centrosomes. Note that cytoplasmic AIR-1 is not depicted in this figure but likely contributes to overall AIR-1 activity. Red: NPP-3; light blue: lamina; gray lines: microtubules; filled line: intact NPP-3 signal; dashed line: disrupted NPP-3 signal. Centrosomes and AIR-1 promote NPP-3 local loss from the NE, potentially facilitating NEBD and timely mitotic entry.