Frog oocyte nuclei are huge: 100,000 somatic nuclei could fit inside them. With size comes the threat of rupture. Markus Bohnsack, Dirk Görlich, and colleagues (Universität Heidelberg, Germany) find that these nuclei are protected from breakage by a network of intranuclear actin filaments.
The German team had previously defined exportin 6 (Exp6) as a nuclear export protein with only one known cargo: β-actin. “I asked my post-doc to do the most boring experiment—to test if exportin also exported α-actin and γ-actin,” says Görlich. “The experiment was not just boring but very frustrating—he couldn't see any export of any substrate.”
Export failed because Bohnsack was using frog oocytes, and this cell type turns off Exp6 production. Adding back Exp6 restored actin export but made the nuclei so fragile that they could rarely be isolated intact. “It was this series of frustrations that got us into something very interesting,” says Görlich.
The fragility arose because oocytes with Exp6 became like all other known cell types: they no longer accumulated enough actin in their nuclei to make actin filaments. In untreated oocytes, however, painstaking fixation revealed heavily branched nuclear actin filaments.
One oocyte nucleus is packed with a huge store of proteins, including enough histones for the DNA of ∼15,000 cells. The resulting gigantic size and fragility are counteracted by a filamentous network that restores sturdiness. Görlich now hopes to reconstitute the network formation in vitro, and to identify the proteins that help actin to form this structure.