What Filaments Are Involved In Cytokinesis

Cytokinesis, the final act of cell division, is a carefully orchestrated process that ensures the faithful segregation of duplicated chromosomes and the partitioning of the cellular contents into two distinct daughter cells. At the heart of this division lies a dynamic interplay of protein filaments, primarily actin and myosin, that drive the physical separation of the cell. Understanding the specific filaments involved and their roles is crucial for comprehending the fundamental mechanisms underlying cell division and its importance in growth, development, and disease.

The Central Role of the Contractile Ring

The key player in animal cell cytokinesis is the contractile ring, a transient structure that forms at the equator of the dividing cell, precisely midway between the segregated chromosomes. This ring, composed mainly of actin filaments and myosin II motor proteins, constricts like a purse string, progressively pinching the cell membrane inward until complete separation occurs.

Actin Filaments: The Scaffold of the Ring

Actin filaments are the most abundant protein in eukaryotic cells, and they form the structural backbone of the contractile ring. These filaments are polymers of the protein actin, and they possess a dynamic nature, constantly undergoing assembly and disassembly.

• Assembly and Dynamics: The formation of actin filaments is a complex process involving the polymerization of individual actin monomers into long, helical structures. This polymerization is driven by the hydrolysis of ATP, which provides the energy for the addition of new monomers to the filament ends. The filaments exhibit polarity, with a "plus" end that grows more rapidly and a "minus" end that disassembles more readily. This dynamic instability allows for rapid remodeling of the actin network during cytokinesis.
• Organization: Within the contractile ring, actin filaments are organized into a tightly packed array that runs circumferentially around the cell equator. This organization is achieved through the action of various actin-binding proteins, including formin and alpha-actinin. Formins nucleate the formation of new actin filaments and promote their elongation, while alpha-actinin cross-links the filaments into bundles, providing structural support to the ring.
• Function: The primary function of actin filaments in cytokinesis is to provide a track for myosin II motor proteins to move along. As myosin II molecules move along the actin filaments, they generate a contractile force that pulls the filaments together, causing the ring to constrict. Additionally, actin filaments contribute to the structural integrity of the ring, preventing it from collapsing or buckling during constriction.

Myosin II: The Molecular Motor

Myosin II is a motor protein that interacts with actin filaments to generate force. It is composed of two heavy chains and two pairs of light chains. The heavy chains contain the motor domain, which binds to actin and hydrolyzes ATP to generate movement. The light chains regulate the activity of the motor domain.

• Mechanism of Action: Myosin II molecules bind to actin filaments and use the energy from ATP hydrolysis to "walk" along the filaments. This walking motion involves a cycle of binding, detachment, and re-binding to the actin filament. As myosin II molecules move along the actin filaments in the contractile ring, they pull the filaments towards each other, generating a contractile force.
• Regulation: The activity of myosin II is tightly regulated during cytokinesis. This regulation is primarily controlled by the phosphorylation of the myosin II light chains. Phosphorylation of the light chains by myosin light chain kinase (MLCK) activates myosin II, allowing it to bind to actin and generate force. Dephosphorylation of the light chains by myosin light chain phosphatase (MLCP) inactivates myosin II, causing it to detach from actin.
• Function: Myosin II is the main force-generating protein in cytokinesis. By walking along actin filaments and pulling them together, myosin II drives the constriction of the contractile ring and the physical separation of the cell. The precise control of myosin II activity is essential for ensuring that cytokinesis occurs at the right time and in the right place.

Other Important Filament-Associated Proteins

While actin and myosin II are the main players in cytokinesis, other filament-associated proteins also play crucial roles in regulating the assembly, organization, and function of the contractile ring. These proteins include:

• Anillin: Anillin is a scaffolding protein that binds to both actin and myosin II, as well as other proteins involved in cytokinesis. It helps to organize and stabilize the contractile ring, and it also plays a role in linking the ring to the cell membrane.
• Septins: Septins are a family of GTP-binding proteins that form filaments at the cell division site. They act as a scaffold, recruiting other proteins to the contractile ring and regulating its assembly and constriction.
• RhoA: RhoA is a small GTPase that acts as a master regulator of cytokinesis. It activates various downstream effectors, including MLCK, which phosphorylates and activates myosin II.
• Profilin: Profilin is an actin-binding protein that promotes the polymerization of actin monomers into filaments. It helps to maintain the pool of available actin monomers and ensures that the contractile ring can assemble rapidly.
• Cofilin: Cofilin is another actin-binding protein that promotes the disassembly of actin filaments. It helps to remodel the actin network during cytokinesis and to ensure that the ring constricts evenly.

The Process of Cytokinesis: A Step-by-Step Breakdown

Cytokinesis is a dynamic process that can be divided into several distinct stages:

1. Initiation: The initiation of cytokinesis is triggered by signals from the mitotic spindle, which ensures that chromosome segregation is complete before cell division begins. These signals activate RhoA, which in turn activates downstream effectors that promote the assembly of the contractile ring.
2. Assembly: The contractile ring assembles at the cell equator, midway between the segregated chromosomes. This assembly process involves the recruitment of actin filaments, myosin II, and other filament-associated proteins to the division site.
3. Constriction: The contractile ring constricts, progressively pinching the cell membrane inward. This constriction is driven by the force generated by myosin II walking along actin filaments.
4. Membrane Ingress: As the contractile ring constricts, the cell membrane invaginates inward, forming a cleavage furrow. This process requires the coordinated action of actin filaments, myosin II, and other proteins that remodel the cell membrane.
5. Abscission: The final stage of cytokinesis is abscission, in which the two daughter cells are physically separated. This process involves the severing of the intercellular bridge that connects the two cells.

Cytokinesis in Plant Cells: A Different Approach

While animal cells use a contractile ring to divide, plant cells employ a different mechanism known as cell plate formation.

The Phragmoplast: A Plant-Specific Structure

Instead of a contractile ring, plant cells form a structure called the phragmoplast. The phragmoplast is a complex assembly of microtubules, actin filaments, and vesicles that forms in the middle of the dividing cell.

• Microtubules: Microtubules are the main structural component of the phragmoplast. They originate from the remnants of the mitotic spindle and serve as tracks for the transport of vesicles to the division site.
• Actin Filaments: Actin filaments are also present in the phragmoplast, although their role is less well understood than in animal cell cytokinesis. They may contribute to the organization and stabilization of the phragmoplast.
• Vesicles: Vesicles are small, membrane-bound sacs that carry cell wall materials to the division site. These vesicles fuse together to form the cell plate, which eventually develops into a new cell wall that separates the two daughter cells.

Cell Plate Formation: Building a New Wall

The process of cell plate formation involves the following steps:

1. Vesicle Transport: Vesicles carrying cell wall materials are transported to the phragmoplast along microtubules.
2. Vesicle Fusion: The vesicles fuse together to form a tubular network.
3. Cell Plate Maturation: The tubular network matures into a flattened, disc-shaped structure called the cell plate.
4. Cell Wall Formation: The cell plate gradually develops into a new cell wall that separates the two daughter cells.

The Significance of Cytokinesis

Cytokinesis is an essential process for all dividing cells. It ensures that each daughter cell receives a complete set of chromosomes and the necessary cellular components to survive and function. Errors in cytokinesis can lead to various problems, including:

• Aneuploidy: Aneuploidy is a condition in which cells have an abnormal number of chromosomes. This can occur if chromosomes are not properly segregated during cell division, leading to one daughter cell receiving too many chromosomes and the other receiving too few.
• Multinucleation: Multinucleation is a condition in which cells have more than one nucleus. This can occur if cytokinesis fails to complete, resulting in a single cell with multiple nuclei.
• Tumor Formation: Errors in cytokinesis have been implicated in the development of cancer. Aneuploidy and multinucleation can disrupt cell cycle control and promote uncontrolled cell growth.

Cytokinesis: A Target for Cancer Therapy

Given the importance of cytokinesis in cell division and its potential role in cancer development, it has become an attractive target for cancer therapy. Several drugs that disrupt cytokinesis are currently under development or in clinical trials. These drugs target various components of the contractile ring or the phragmoplast, aiming to selectively kill cancer cells by preventing them from dividing.

Conclusion

Cytokinesis is a fundamental process that ensures the faithful segregation of cellular contents during cell division. In animal cells, this process is driven by the contractile ring, a dynamic structure composed of actin filaments and myosin II motor proteins. These filaments work together to constrict the cell membrane and physically separate the two daughter cells. In plant cells, cytokinesis involves the formation of a cell plate, a new cell wall that is constructed in the middle of the dividing cell. Understanding the intricate mechanisms of cytokinesis is essential for comprehending the fundamental processes of life and for developing new strategies to treat diseases such as cancer.