An F-actin shell ruptures the nuclear envelope by sorting pore-dense and pore-free membranes in meiosis of starfish oocytes

Natalia Wesolowska, Pedro Machado, Celina Geiss, Hiroshi Kondo, Masashi Mori, Yannick Schwab, Peter Lenart

Posted on: 19 December 2018

Preprint posted on 28 November 2018

Watch out! F-actin spikes push against the nuclear envelope to separate nuclear pores and lead to nuclear envelope breakdown

Selected by Maiko Kitaoka

Categories: cell biology


The nuclear envelope is a specialized structure composed of membrane proteins that protects the nuclear content from the cytoplasm. In interphase, this compartmentalization of nuclear vs. cytoplasmic content allows the cell to regulate gene expression and transport. However, the nuclear envelope must break down during every cell division in order for the microtubule cytoskeleton to contact the chromosomes and allow for faithful segregation. This occurs in two phases: First, the nuclear envelope is gradually permeabilized as nuclear pore complexes and other proteins are disassembled by phosphorylation signals, thus weakening the nuclear envelope and slowly allowing proteins to leak in and out. Second, the nuclear envelope suddenly ruptures so that the cytoplasm mixes quickly and completely with the nuclear contents. This phase is visible with light microscopy and is referred to as nuclear envelope breakdown (NEBD). Following rapid mitotic spindle formation and chromosome segregation, the nuclear envelope must then be quickly reassembled to ensure the integrity of the genome following cell division.

The Lenart lab has previously demonstrated the importance of the actin cytoskeleton in rupturing the nuclear envelope due to the presence of a transient F-actin shell on the nuclear envelope. Now, Wesolowska et al use starfish oocytes to continue the investigation into the role of this F-actin shell in mediating nuclear membrane rupture. Here, they use confocal and super-resolution microscopy as well as correlated electron microscopy to observe the rapid and dramatic changes in nuclear envelope morphology to find that the F-actin shell on the inner surface of the nuclear envelope projects spikes into the nuclear membranes. They propose that this can generate force and pull apart the nuclear membranes to destabilize the structure during NEBD.

Key findings

By carefully analyzing samples at different stages of nuclear envelope morphological changes, the authors confirmed previous observations that the lamina network remains intact after nuclear envelope rupture, though it folds during NEBD. The nuclear envelope forms a separate layer from the F-actin shell, while the lamina network co-localized with actin by phalloidin staining. This indicates that the lamina serves as the scaffold for F-actin to assemble, but the nuclear membranes are detached from the lamina by the F-actin shell.

Upon closer investigation, the group found that the F-actin shell forms spikes that go through the nuclear membrane. Super-resolution STED microscopy revealed that these F-actin spikes are 0.5-2 µm in length and 0.1 µm apart from each other. After NEBD, the nuclear envelope appeared to be “floating” above the laminar network, a detachment that is dependent on the F-actin shell.

An example of the dramatic F-actin spikes that appear to pierce through the nuclear envelope (marked by nuclear pore complexes). From Figure 2.


Due to technical limitations of preserving both filamentous actin and fine membrane structures, the authors turned to correlative light and electron microscopy to examine these spikes at the membrane in further detail. Strikingly, the EM images showed that the F-actin spikes were localized to regions of nuclear membrane that had no nuclear pore complexes. Pore-free areas were in turn adjacent to pore-dense regions. This suggested that growing gaps between pore complexes are extruded by the F-actin spikes, sorting the nuclear envelope globally to pore-free and pore-dense regions even when the membrane is initially intact.

An EM section with regions that are pore-free with F-actin spikes and regions with nuclear pores. From Figure 3.


In addition to the F-actin spikes, the authors also observed nucleoplasmic bodies that formed beneath the nuclear envelope. These bodies seemed reminiscent of several potential processes, including aggregation of nuclear pore complexes into the nucleoplasm and membrane vesicle formation. The authors suggest that these bodies may be inverted nuclear envelope tubules filled with cytoplasm, which is also indicated by the presence of ribosomes. However, their exact composition and purpose still remain unclear.

To conclude, Wesolowska et al used advanced light and electron microscopy to determine that F-actin spikes push against the nuclear membrane. This separates the pore-free regions from the nuclear lamina, while the pores accumulate between F-actin spikes. Together, this causes the membrane to buckle and invaginate as it weakens, eventually rupturing and causing complete nuclear envelope breakdown.

Model demonstrating how F-actin spikes cause dissociation of the lamina network and use the pore-free regions to cause nuclear envelope rupturing. From Figure 5.


Questions for the authors

How do the F-actin spikes “know” where to push on the nuclear membrane? They need to polymerize actin in pore-free regions, so how is that detected? Or do the spikes polymerize randomly until they find an area without nuclear pores?

What mechanism(s) connect the phosphorylation-based disassembly of nuclear pore complexes and the actin polymerization necessary to create these F-actin spikes that eventually causes nuclear envelope rupture?

If the nucleoplasmic bodies are inverted nuclear envelope tubules as suggested, how do they help to mediate NEBD, and what happens to them after NEBD?

Tags: actin, cell biology, meiosis, nebd, nuclear envelope, oocytes, starfish


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Author's response

Peter Lenart shared

How do the F-actin spikes “know” where to push on the nuclear membrane? They need to polymerize actin in pore-free regions, so how is that detected? Or do the spikes polymerize randomly until they find an area without nuclear pores?

LP: We do not think the spikes know where to push. We think that the Arp2/3 complex gets activated at random locations along the lamina causing local bursts of actin polymerization. This then pushes the pores aside at that location.

What mechanism(s) connect the phosphorylation-based disassembly of nuclear pore complexes and the actin polymerization necessary to create these F-actin spikes that eventually causes nuclear envelope rupture?

LP: Careful analysis of entry of dextrans and other data suggest that actin polymerization is likely triggered when slow mixing (driven by phosphorylation-based disassembly) reaches a certain threshold. For example, the Arp2/3 complex is strictly cytoplasmic in interphase, but it will slowly start leaking into the nucleus during slow disassembly. When nuclear Arp2/3 reaches a certain threshold concentration, actin polymerization may be triggered. However, our data suggest that this is unfortunately not this simple and driven by Arp2/3 alone, but it is likely to involve a set of additional components.

If the nucleoplasmic bodies are inverted nuclear envelope tubules as suggested, how do they help to mediate NEBD, and what happens to them after NEBD?

LP: We do not yet know what is the fate and function of nucleoplasmic bodies. We suspect that in oocytes that store an extreme amount of pre-assembled nuclear pores these may serve as a specialized storage compartment (unlike somatic cells, in which nuclear pore components are fully dispersed in the ER).

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