Cytokinesis Overlaps With Which Phase Of Mitosis

Cytokinesis, the final act in cell division, ensures that one cell physically divides into two distinct daughter cells. While often conceptually separated from mitosis, the process of cytokinesis is intricately interwoven with the later stages of mitosis. Understanding the overlap between cytokinesis and mitosis is crucial for comprehending the fidelity and coordination of cell division.

The Mitotic Dance: A Quick Review

Before diving into the overlap, let's recap the phases of mitosis:

• Prophase: Chromosomes condense, and the mitotic spindle begins to form.
• Prometaphase: The nuclear envelope breaks down, and spindle microtubules attach to the chromosomes at the kinetochores.
• Metaphase: Chromosomes align at the metaphase plate, ensuring each daughter cell receives a complete set.
• Anaphase: Sister chromatids separate and move to opposite poles of the cell.
• Telophase: Chromosomes arrive at the poles, the nuclear envelope reforms, and the chromosomes decondense.

Cytokinesis: Dividing the Spoils

Cytokinesis is the process by which the cytoplasm of a single eukaryotic cell divides into two daughter cells. It typically begins during anaphase and continues through telophase, effectively overlapping with the final stages of mitosis. In animal cells, cytokinesis is characterized by the formation of a contractile ring composed of actin and myosin filaments, which constricts the cell at the equator, eventually pinching it into two. In plant cells, a cell plate forms in the middle of the cell and grows outward to create a new cell wall that divides the cell.

The Overlap: Anaphase and Telophase

The key overlap between cytokinesis and mitosis occurs during anaphase and telophase.

Anaphase: The Initial Steps

The initiation of cytokinesis is tightly linked to the events of anaphase. As the sister chromatids separate and move towards opposite poles, signals are triggered that initiate the assembly of the contractile ring in animal cells, or the formation of the cell plate in plant cells. Several key events occur during anaphase that prepare the cell for division:

• Spindle Positioning: The mitotic spindle, responsible for chromosome segregation, plays a crucial role in determining the site of cytokinesis. The position of the spindle midzone, the region between the separating chromosomes, signals the location where the contractile ring will form. This ensures that the cell divides precisely between the two sets of chromosomes.
• Signaling Pathways: Anaphase is marked by the activation of various signaling pathways that are essential for initiating cytokinesis. These pathways involve a cascade of protein interactions and modifications that ultimately lead to the recruitment and activation of proteins required for contractile ring assembly. One of the key players is the RhoA GTPase, which acts as a molecular switch, activating downstream effectors that promote actin and myosin assembly.
• Midzone Formation: The spindle midzone is not just a passive bystander; it actively participates in cytokinesis. It contains a complex array of proteins that regulate the assembly and stability of the contractile ring. These proteins include the centralspindlin complex, which is crucial for recruiting other components of the cytokinesis machinery to the midzone.

Telophase: Completion and Separation

Cytokinesis continues and is largely completed during telophase. As the nuclear envelope reforms around the separated chromosomes, the contractile ring continues to constrict in animal cells, or the cell plate expands in plant cells. The final steps of cytokinesis involve the complete separation of the two daughter cells:

• Contractile Ring Constriction (Animal Cells): The contractile ring, composed of actin and myosin filaments, progressively constricts, pulling the plasma membrane inward. This process is driven by the sliding of actin filaments relative to each other, powered by the motor protein myosin. As the ring constricts, the cell membrane invaginates, forming a cleavage furrow that deepens until the cell is pinched into two.
• Cell Plate Formation (Plant Cells): In plant cells, cytokinesis involves the formation of a cell plate, a new cell wall that grows outward from the center of the cell. The cell plate is assembled from vesicles containing cell wall components, which are transported to the division plane along microtubules. These vesicles fuse, forming a flattened, disc-like structure that gradually expands until it reaches the existing cell wall, dividing the cell into two.
• Midbody Formation: In animal cells, the final stage of cytokinesis involves the formation of a midbody, a dense structure that connects the two daughter cells. The midbody contains remnants of the mitotic spindle and contractile ring components. It serves as a bridge between the cells until abscission, the final severing of the intercellular bridge, occurs.

Why the Overlap Matters: Ensuring Fidelity

The overlap between cytokinesis and anaphase/telophase is not accidental; it is essential for ensuring the fidelity of cell division. This coordination prevents premature or asynchronous division, which can lead to aneuploidy (an abnormal number of chromosomes) and other genomic instabilities.

• Coordination: The close temporal relationship between chromosome segregation and cell division ensures that each daughter cell receives a complete and accurate set of chromosomes before cytokinesis physically separates them.
• Error Correction: The overlap allows for error correction mechanisms to operate. If chromosome segregation is not completed correctly during anaphase, the signals that initiate cytokinesis can be delayed or inhibited, providing an opportunity for the cell to correct the error before proceeding with division.
• Spatial Accuracy: The mitotic spindle plays a crucial role in determining the site of cytokinesis, ensuring that the cell divides precisely between the two sets of chromosomes. This spatial coordination is essential for maintaining the correct chromosome number and genetic content in the daughter cells.

The Molecular Players: Orchestrating the Division

Several key molecular players are involved in coordinating the overlap between cytokinesis and mitosis:

• RhoA: A small GTPase that acts as a master regulator of contractile ring assembly and constriction.
• Anaphase-Promoting Complex/Cyclosome (APC/C): A ubiquitin ligase that triggers the metaphase-to-anaphase transition and regulates the timing of cytokinesis.
• Centralspindlin: A protein complex that localizes to the spindle midzone and recruits other components of the cytokinesis machinery.
• Microtubules: Dynamic polymers that form the mitotic spindle and play a crucial role in spindle positioning and cell plate formation.
• Actin and Myosin: The building blocks of the contractile ring in animal cells, responsible for generating the force that constricts the cell.

Research and Clinical Significance

Understanding the intricacies of the cytokinesis-mitosis overlap has significant implications for both basic research and clinical applications:

• Cancer Biology: Errors in cytokinesis can lead to aneuploidy and genomic instability, which are hallmarks of cancer. Understanding the molecular mechanisms that regulate cytokinesis can provide insights into the development and progression of cancer, as well as potential targets for cancer therapy.
• Developmental Biology: Proper cell division is essential for embryonic development and tissue homeostasis. Disruptions in cytokinesis can lead to developmental defects and contribute to various diseases.
• Drug Discovery: Several drugs that target microtubules and other components of the mitotic spindle are used in cancer chemotherapy. Understanding the effects of these drugs on cytokinesis can help optimize their use and minimize side effects.
• Basic Cell Biology: Studying the coordination between mitosis and cytokinesis provides fundamental insights into the mechanisms that govern cell division, one of the most fundamental processes in biology.

Cytokinesis in Different Organisms

While the fundamental principles of cytokinesis are conserved across eukaryotes, there are some notable differences in the details of the process in different organisms.

Animal Cells

As mentioned earlier, animal cells undergo cytokinesis through the formation of a contractile ring. This ring is composed primarily of actin and myosin filaments and assembles at the equatorial plane of the cell, guided by signals from the mitotic spindle.

• Contractile Ring Assembly: The assembly of the contractile ring is a highly dynamic process that involves the recruitment of numerous proteins to the division site. RhoA, a small GTPase, plays a central role in this process by activating downstream effectors that promote actin polymerization and myosin activation.
• Cleavage Furrow Formation: As the contractile ring constricts, the plasma membrane invaginates, forming a cleavage furrow. The furrow deepens until the two daughter cells are connected only by a narrow intercellular bridge containing the midbody.
• Abscission: The final step of cytokinesis in animal cells is abscission, the severing of the intercellular bridge. This process is regulated by a complex interplay of signaling pathways and involves the recruitment of ESCRT-III (Endosomal Sorting Complexes Required for Transport III) machinery to the midbody.

Plant Cells

Plant cells, with their rigid cell walls, employ a different mechanism for cytokinesis. Instead of a contractile ring, they form a cell plate, a new cell wall that grows outward from the center of the cell.

• Cell Plate Formation: The cell plate is assembled from vesicles containing cell wall components, which are transported to the division plane along microtubules. These vesicles fuse, forming a flattened, disc-like structure that gradually expands until it reaches the existing cell wall.
• Phragmoplast: The formation of the cell plate is guided by the phragmoplast, a structure composed of microtubules and associated proteins. The phragmoplast expands outward, delivering vesicles to the growing edge of the cell plate.
• Cell Wall Completion: Once the cell plate reaches the existing cell wall, it fuses with it, completing the separation of the two daughter cells. The cell plate then matures into a new cell wall, providing structural support for the newly formed cells.

Yeast

Yeast cells also undergo cytokinesis through the formation of a contractile ring, but the process is somewhat different from that in animal cells.

• Septum Formation: In yeast, cytokinesis involves the formation of a septum, a new cell wall that grows inward from the cell periphery. The septum is composed of chitin, a polysaccharide that is also found in the exoskeletons of insects and crustaceans.
• Contractile Ring Assembly: The contractile ring in yeast is similar to that in animal cells, consisting of actin and myosin filaments. However, the assembly of the ring is regulated by different signaling pathways.
• Cell Separation: Once the septum is complete, the two daughter cells separate. This process involves the enzymatic degradation of the septum, allowing the cells to physically separate.

Factors Influencing Cytokinesis

Cytokinesis is a tightly regulated process that is influenced by a variety of factors, including:

• Cell Type: Different cell types may have different requirements for cytokinesis, depending on their function and environment.
• Cell Cycle Stage: Cytokinesis is tightly coupled to the cell cycle and is regulated by cell cycle checkpoints.
• Environmental Conditions: Environmental factors such as temperature, pH, and nutrient availability can affect cytokinesis.
• Genetic Mutations: Mutations in genes involved in cytokinesis can lead to defects in cell division and contribute to disease.

Troubleshooting Cytokinesis Issues

Problems during cytokinesis can have significant consequences for cell health and organismal development. Here are some issues that might arise and potential solutions:

• Incomplete Cytokinesis: If the contractile ring fails to fully constrict or the cell plate does not completely form, the daughter cells may remain connected. This can lead to the formation of multinucleated cells or cells with abnormal chromosome numbers.
  • Troubleshooting: Ensure that all components of the cytokinesis machinery are functioning properly. Check the levels and activity of RhoA, actin, myosin, and other key proteins. Consider using drugs that promote actin polymerization or myosin activation.
• Premature Cytokinesis: If cytokinesis begins before chromosome segregation is complete, the daughter cells may receive an unequal number of chromosomes. This can lead to aneuploidy and genomic instability.
  • Troubleshooting: Ensure that the cell cycle checkpoints are functioning properly. Check the levels and activity of proteins involved in the spindle assembly checkpoint. Consider using drugs that delay the onset of anaphase.
• Misplaced Cytokinesis: If the contractile ring or cell plate forms in the wrong location, the daughter cells may not be properly separated. This can lead to the formation of cells with abnormal shapes or sizes.
  • Troubleshooting: Ensure that the mitotic spindle is properly positioned. Check the levels and activity of proteins involved in spindle positioning. Consider using drugs that disrupt microtubule dynamics.

Conclusion

Cytokinesis overlaps significantly with anaphase and telophase of mitosis. This overlap is not a mere coincidence but a tightly regulated process essential for ensuring accurate chromosome segregation and faithful cell division. The molecular players involved in this coordination, such as RhoA, APC/C, and centralspindlin, orchestrate the complex events that lead to the physical separation of the two daughter cells. Understanding the intricacies of this overlap is crucial for advancing our knowledge of cell biology, cancer biology, and developmental biology, and it holds promise for the development of new therapies for various diseases. By delving deeper into the mechanisms that govern cytokinesis, we can gain valuable insights into the fundamental processes that underlie life itself.