Abstract
The nucleus of oocytes (germinal vesicle) is unusually large and its nuclear envelope (NE) is densely packed with nuclear pore complexes (NPCs) that are stockpiled for embryonic development. We showed that breakdown of this specialized NE is mediated by an Arp2/3-nucleated F-actin 'shell' in starfish oocytes, in contrast to microtubule-driven tearing in mammalian fibroblasts. Here, we address the mechanism of F-actin-driven NE rupture by correlated live-cell, super-resolution and electron microscopy. We show that actin is nucleated within the lamina, sprouting filopodia-like spikes towards the nuclear membranes. These F-actin spikes protrude pore-free nuclear membranes, whereas the adjoining stretches of membrane accumulate NPCs that are associated with the still-intact lamina. Packed NPCs sort into a distinct membrane network, while breaks appear in ER-like, pore-free regions. We reveal a new function for actin-mediated membrane shaping in nuclear rupture that is likely to have implications in other contexts, such as nuclear rupture observed in cancer cells.
Highlights
The nuclear envelope (NE), composed of inner and outer nuclear membranes, is a specialized subcompartment of the endoplasmic reticulum (ER) that separates the nucleus and the cytoplasm in eukaryotic cells
We have shown previously that NE rupture, characterized by a wave-like entry of large cytoplasmic molecules into the nucleus, is mediated by a transient F-actin shell on the inner side of the NE, which is nucleated by the Arp2/3 complex (Mori et al, 2014)
It became obvious to us that we needed to address what happens in the 30–45 s period between the start of actin assembly and NE rupture, as this appears to be a critical moment in F-actin-driven NE rupture
Summary
The nuclear envelope (NE), composed of inner and outer nuclear membranes, is a specialized subcompartment of the endoplasmic reticulum (ER) that separates the nucleus and the cytoplasm in eukaryotic cells. It is likely that the mechanical properties of the NE are affected, that is the NE is weakened and destabilized as a result of the phosphorylation of lamins and lamina-associated proteins (Ungricht and Kutay, 2017) During this first phase of NEBD, the overall structure of the NE (as observed by electron microscopy (EM)) is still intact and the compartmentalization of large protein complexes (e.g. ribosomes and microtubules) is maintained (Terasaki et al, 2001; Lenart et al, 2003). These NPC-dense conglomerates invaginate and sort into the NPC-rich membrane network, while breaks appear on the pore-free regions
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