Nuclear Envelope Mitosis: Processes and Key Breakdowns

The nuclear envelope is a critical barrier that separates the nucleus from the cytoplasm, maintaining genomic integrity and regulating molecular exchange. During mitosis in eukaryotic cells, this structure must disassemble to allow chromosome segregation before reassembling around the daughter nuclei. Disruptions in this process can lead to genomic instability, which is linked to various diseases, including cancer.

Understanding how the nuclear envelope breaks down and reforms provides insight into cell division mechanics and potential therapeutic targets.

Structural Components

The nuclear envelope is a double-membrane structure that encases the nucleus, providing both a physical barrier and a dynamic interface for molecular trafficking. It consists of an outer membrane, which is continuous with the rough endoplasmic reticulum (ER), and an inner membrane, which is lined by a dense protein network known as the nuclear lamina. This lamina, composed primarily of A- and B-type lamins, maintains nuclear shape and anchors chromatin. Its regulated disassembly is essential for mitotic progression.

Nuclear pore complexes (NPCs), large multiprotein assemblies embedded within the envelope, mediate molecular transport between the nucleus and cytoplasm. Composed of nucleoporins, NPCs selectively allow the passage of proteins, RNAs, and ribonucleoprotein complexes while preventing uncontrolled diffusion. During interphase, they regulate gene expression by controlling RNA export and transcription factor import. Their disassembly during mitosis ensures transport functions are suspended to allow chromosome segregation.

The outer membrane is functionally integrated with the ER, sharing a continuous lipid bilayer and associated ribosomes, enabling rapid membrane remodeling. The inner membrane contains specialized proteins such as emerin, LBR (lamin B receptor), and SUN-domain proteins, which interact with the lamina and chromatin. These proteins contribute to nuclear positioning and mechanotransduction, linking the nucleus to the cytoskeleton through the LINC (linker of nucleoskeleton and cytoskeleton) complex. Disrupting these interactions is necessary for nuclear envelope breakdown, allowing chromatin to detach from the inner membrane.

Regulation of Envelope Disassembly

Nuclear envelope disassembly during mitosis is orchestrated through precisely timed molecular events. Cyclin-dependent kinase 1 (CDK1), in complex with cyclin B, triggers phosphorylation events that target nuclear envelope proteins. This weakens interactions between the lamina, inner membrane proteins, and chromatin, initiating envelope breakdown. CDK1-mediated phosphorylation of lamins depolymerizes the lamina, causing it to detach from the inner membrane and lose structural integrity.

Other kinases, such as polo-like kinase 1 (PLK1) and Aurora B, further regulate disassembly. PLK1 phosphorylates NPC components, leading to their dissociation and degradation by the proteasome. This dismantling eliminates the selective barrier between the nucleus and cytoplasm, allowing mitotic regulators access to nuclear contents. Aurora B disrupts interactions between inner nuclear membrane proteins and chromatin, promoting membrane vesiculation.

Membrane remodeling is another essential aspect, driven by ER-associated proteins. The outer nuclear membrane, continuous with the ER, reorganizes as membrane reservoirs are mobilized. Reticulon proteins and atlastins shape fragmented nuclear membranes, aiding redistribution. The AAA-ATPase VPS4 promotes the extraction of nucleoporins and membrane-associated factors from disassembling NPCs. These events ensure nuclear envelope components remain dynamic and available for reassembly.

Sequence of Breakdown

As mitosis begins, the nuclear envelope undergoes structural changes to facilitate disassembly. Phosphorylation of nuclear lamins destabilizes the lamina, leading to depolymerization and loss of nuclear rigidity. The inner membrane detaches from chromatin, while NPCs disassemble as nucleoporins dissociate. This eliminates the selective barrier between the nucleus and cytoplasm, allowing mitotic regulators uninhibited access to nuclear components.

As the lamina dissolves and NPCs disassemble, the nuclear membranes lose cohesion. The outer and inner membranes vesiculate into discrete fragments, influenced by interactions with the ER, which absorbs portions of the nuclear envelope. This redistribution ensures membrane material remains available for reassembly. Molecular motors and cytoskeletal elements disperse nuclear envelope fragments, preventing premature aggregation that could interfere with mitotic progression. Chromatin must be fully exposed to spindle microtubules for accurate segregation.

Steps in Envelope Reformation

As mitosis nears completion, the nuclear envelope is reconstructed around the daughter chromosomes. Membrane vesicles and tubular elements from the ER coalesce around chromatin, guided by interactions between inner nuclear membrane proteins and decondensing chromosomes. Barrier-to-autointegration factor (BAF) plays a key role in bridging chromatin to membrane structures, ensuring controlled reassembly.

Once membranes enclose chromatin, nuclear proteins are reintroduced to restore compartmentalization. Dephosphorylated lamins repolymerize, forming a supportive meshwork beneath the inner membrane. This lamina network stabilizes the envelope and influences nuclear shape. Meanwhile, nuclear pore complexes (NPCs) reassemble in a stepwise manner, with nucleoporins such as Nup153 and Nup107-160 complexes incorporating first to establish pore functionality. The precise timing of NPC reformation ensures selective transport resumes efficiently.