Temporal Regulation of Lipin Activity Diverged to Account for Differences in Mitotic Programs

Eukaryotes remodel the nucleus during mitosis using a variety of mechanisms that differ in the timing and the extent of nuclear envelope (NE) breakdown. Here, we probe the principles enabling this functional diversity by exploiting the natural divergence in NE management strategies between the related fission yeasts Schizosaccharomyces pombe and Schizosaccharomyces japonicus [1–3]. We show that inactivation of Ned1, the phosphatidic acid phosphatase of the lipin family, by CDK phosphorylation is both necessary and sufficient to promote NE expansion required for “closed” mitosis in S. pombe. In contrast, Ned1 is not regulated during division in S. japonicus, thus limiting membrane availability and necessitating NE breakage. Interspecies gene swaps result in phenotypically normal divisions with the S. japonicus lipin acquiring an S. pombe-like mitotic phosphorylation pattern. Our results provide experimental evidence for the mitotic regulation of phosphatidic acid flux and suggest that the regulatory networks governing lipin activity diverged in evolution to give rise to strikingly dissimilar mitotic programs. •Lipin phosphorylation by CDK drives mitotic nuclear envelope expansion in S. pombe•CDK-dependent lipin phosphorylation is required for closed mitosis•Lipin is not regulated by mitotic CDK in the related species S. japonicus•Interspecies gene swaps reveal species-specific trans-regulation of lipin activity Using closely related yeasts, Makarova et al. uncover a molecular basis for variability in nuclear envelope expansion during mitosis. They show that cells undergoing closed mitosis expand their nuclear envelope prior to division by entraining inactivation of the phosphatidic acid flux regulator lipin to high CDK activity.