Prometaphase serves as the dynamic intermediate stage of mitosis, transitioning the cell from the early preparations of prophase to the highly organized alignment of metaphase. Mitosis itself is the process of nuclear division in eukaryotic cells, which ultimately generates two genetically identical daughter cells. This phase is characterized by a dramatic shift in cellular architecture, allowing the machinery of cell division to access the duplicated genetic material.
The main objective of this stage is to establish the physical connections between the condensed chromosomes and the mitotic spindle fibers. Without these connections, the cell would be unable to accurately separate the sister chromatids, leading to errors in the distribution of genetic information. The events of prometaphase set the stage for the precise, equal segregation of chromosomes that defines the later stages of mitosis.
Nuclear Envelope Fragmentation
The onset of prometaphase in many higher eukaryotes is marked by the complete breakdown of the nuclear envelope. This barrier must disassemble to allow the cytoplasmic mitotic spindle fibers to reach the chromosomes. The nuclear envelope fragments into small, distinct membrane vesicles that disperse throughout the cytoplasm.
The dissolution of the envelope is primarily driven by the mitotic phosphorylation of key structural proteins by activated mitotic kinases. This phosphorylation targets components such as the nuclear lamins, which form the supportive meshwork of the nuclear lamina underlying the inner nuclear membrane. Disassembly of the nuclear lamina releases the structural support, while phosphorylation of Inner Nuclear Membrane (INM) proteins and Nuclear Pore Complex (NPC) subunits causes the entire structure to fall apart.
Once fragmented, the nucleoplasm and cytoplasm mix, exposing the condensed chromosomes to the forming mitotic spindle. The spindle, which has been growing from the centrosomes outside the nucleus, can now enter the former nuclear region. This mixing of components is a fundamental step for “open mitosis,” ensuring the chromosomes are available for capture.
Spindle Fiber Capture
With the nuclear barrier removed, the mitotic spindle microtubules begin a “search and capture” process for the condensed chromosomes. A specialized protein complex, the kinetochore, is the target for these searching microtubules. The kinetochore forms on the centromere region of each sister chromatid, effectively acting as a docking station for the spindle fibers.
Each duplicated chromosome consists of two sister chromatids, and therefore possesses two kinetochores, one on each chromatid, facing opposite poles of the cell. The microtubules that successfully attach to a kinetochore are called kinetochore microtubules, forming a structure known as a K-fiber. Initially, the dynamic microtubules may make unstable lateral attachments to the side of the kinetochore.
These initial, lateral attachments are often mediated by motor proteins like cytoplasmic dynein and Cenp-E, which help transport the chromosome along the microtubule toward a spindle pole. The ultimate goal is the establishment of a stable end-on attachment, where the plus end of the microtubule is directly embedded within the kinetochore structure. This stable connection, known as bipolar attachment or bi-orientation, is a prerequisite for moving into the next stage of mitosis.
Chromosome Movement to the Center
The successful attachment of kinetochore microtubules initiates the process of chromosome movement toward the cell’s center, a dynamic process referred to as congression. During congression, chromosomes are subjected to antagonistic pushing and pulling forces from the microtubules emanating from the two opposite spindle poles. This creates a highly agitated, oscillatory motion as the chromosomes are reeled in.
The movement is driven by the coordinated action of motor proteins and the regulated polymerization and depolymerization of the kinetochore microtubules. The combination of these forces and movement pathways gradually pulls and pushes all the chromosomes toward an imaginary central line within the cell. This equatorial plane is known as the metaphase plate.
Prometaphase concludes when every chromosome has achieved stable bi-orientation. This means sister kinetochores are connected to microtubules from opposite poles, and the chromosomes are aligned at the central plane, ready for the separation phase of anaphase.