The nuclear envelope is the double-layered barrier separating the nucleus from the cytoplasm. This structure maintains the distinct environment required for genetic processes. During mitosis, this envelope must be dismantled to allow the precise segregation of chromosomes into two daughter cells. Prophase involves the condensation of chromatin into visible chromosomes. The envelope’s dissolution facilitates the next steps of cell division.
The Nuclear Envelope Breakdown
Immediately following prophase, the cell enters prometaphase, during which the nuclear envelope undergoes Nuclear Envelope Breakdown (NEBD). This breakdown is a rapid event that marks the transition from a closed nucleus to an open cytoplasm for the mitotic machinery. NEBD results in the fragmentation of the double membrane into numerous small vesicles that disperse throughout the cytoplasm.
This fragmentation is required for open mitosis, the type of cell division seen in most higher organisms. Dissolving the nuclear barrier grants the mitotic spindle fibers access to the condensed chromosomes. These spindle fibers, specialized microtubules, must attach to the kinetochores on the chromosomes to align them correctly for separation. Dismantling the envelope allows the spindle fibers to freely enter the former nuclear area to capture the chromosomes.
The components of the nuclear envelope do not simply vanish. The outer membrane, which is continuous with the endoplasmic reticulum (ER), retracts and becomes part of the extensive ER network. Inner nuclear membrane proteins disperse into the ER membrane, while the proteins of the nuclear pore complexes dissociate. This dissolution ensures that the sister chromatids can be properly captured and moved to opposite poles of the cell during anaphase.
Molecular Mechanisms of Disassembly
The trigger for the physical breakdown is the activation of specific regulatory proteins, primarily Cyclin-Dependent Kinases (CDKs). The CDK1-Cyclin B complex becomes highly active at the onset of mitosis and acts as the master switch for disassembly. These kinases initiate the breakdown by adding phosphate groups, a process called phosphorylation, to various structural components of the nuclear envelope.
A major target of phosphorylation is the nuclear lamina, a meshwork of intermediate filaments made of lamin proteins that supports the inner nuclear membrane. CDK1 phosphorylates the nuclear lamins, disrupting the protein-to-protein interactions that hold the filaments together. This causes the entire meshwork to depolymerize, or fall apart. The collapse of this structural support destabilizes the inner nuclear membrane, allowing it to fragment.
CDK1 and other kinases, such as Polo-like kinase 1 (PLK1), also phosphorylate components of the Nuclear Pore Complexes (NPCs). Phosphorylation causes these large protein channels to dissociate into smaller subcomplexes and individual proteins. This simultaneous dismantling of the lamina and the pore complexes ensures the complete fragmentation of the nuclear envelope into mitotic membrane vesicles. Phosphorylation also affects integral inner nuclear membrane proteins, disrupting their association with the chromatin and facilitating their dispersal into the ER.
Reassembly of the Nuclear Envelope
Reassembly of the nuclear envelope is a reversal of the breakdown process and occurs during telophase, after the chromosomes have been separated into two distinct sets. As the cell exits mitosis, the activity of mitotic kinases like CDK1 declines dramatically, primarily due to the degradation of their cyclin partners. The inactivation of these kinases allows phosphatases, enzymes that remove phosphate groups, to become active.
Protein phosphatases, such as PP1 and PP2A, remove the phosphate groups added to the nuclear envelope components during disassembly. This dephosphorylation signals reassembly. Removing phosphate groups from the lamin proteins allows them to repolymerize, forming a new nuclear lamina around each set of separated chromosomes.
The membrane vesicles formed from the fragmented nuclear envelope are recruited to the surface of the decondensing chromosomes. Integral inner nuclear membrane proteins and lamin B proteins target these vesicles to the chromatin surface. The vesicles then fuse laterally, expanding and enclosing the chromosomes to form a continuous double-layered nuclear envelope for each daughter nucleus, restoring the separation between the genetic material and the cytoplasm.