Mall et al. reveal how lipid-making enzymes spur the demolition of the nuclear lamina in mitotic cells.
Before a cell divides, it takes apart the lamina, the protein backing for the nuclear envelope. Cells remove the individual lamin proteins from the structure and save them for later reuse. At least two lamin-phosphorylating kinases, protein kinase C (PKC) and cyclin-dependent kinase 1 (CDK1), stimulate lamina breakdown. Lipid-manufacturing enzymes called lipins are necessary for lamina disassembly, but the mechanics of the process remain unclear.
To tease out the roles of PKC and CDK1, Mall et al. mutated lamin B1 molecules so that they carried fewer phosphorylation sites for the two enzymes. Mutating only the CDK1 sites or a combination of CDK1 and PKC sites progressively slowed lamina breakdown. Blocking both kinases with inhibitors enhanced the delay, indicating that the two enzymes collaborate to take apart the lamina. Relying on more than one enzyme to stimulate lamina disassembly could ensure that cells complete the process promptly, the researchers suggest.
PKC’s involvement suggests a link with lipins because the product of these enzymes, diacylglycerol (DAG), switches on PKC. To determine whether lipins activate PKC during lamina breakdown, the researchers knocked down all three mammalian lipins with RNAi or applied inhibitors. Lamina disassembly slowed dramatically in these cells. But adding DAG to the lipin-depleted cells restored lamina breakdown. The findings suggest that lipins prompt lamina deconstruction by spawning DAG that activates PKC.
