Cleavage Furrow and Its Role in Cell Division
Explore the cleavage furrow's role in cell division, from actomyosin ring assembly to membrane constriction, and how it varies across different cell types.
Cells divide to grow, repair tissues, and reproduce. A key step in this process is the formation of the cleavage furrow, which ensures one cell separates into two daughter cells. This event relies on structural and biochemical mechanisms to function properly.
A closer look at how the cleavage furrow forms and operates highlights its essential role in maintaining life across different organisms.
Role In Cell Division
The cleavage furrow is crucial in the final steps of cell division, ensuring a parent cell separates into two genetically identical daughter cells. This process, known as cytokinesis, begins in the late stages of mitosis or meiosis, when the mitotic spindle directs the furrow’s position. Signals from the central spindle and astral microtubules define the division plane, ensuring equal distribution of cytoplasmic contents and organelles to prevent developmental defects or disease.
Once established, the furrow deepens to partition the cytoplasm. This inward constriction is driven by a contractile network of actin filaments and myosin-II motor proteins, which generate the force needed to pull the plasma membrane inward. This process is regulated by signaling pathways, including RhoA, a small GTPase that orchestrates actin polymerization and myosin activation. Disruptions in these pathways can lead to cytokinetic failure, resulting in multinucleated cells linked to tumorigenesis and other diseases.
As the furrow constricts, intracellular organelles rearrange to ensure proper segregation. The endoplasmic reticulum and Golgi apparatus adapt to the narrowing space, while vesicular trafficking contributes membrane components to support furrow ingression. This coordination is especially critical in embryonic development, where rapid divisions require precise regulation. Studies in model organisms like Caenorhabditis elegans and Drosophila melanogaster show that mutations affecting furrow formation can cause embryonic lethality, underscoring its importance in early development.
Actomyosin Ring Assembly
The actomyosin ring provides the mechanical force for cleavage furrow ingression. Composed of filamentous actin (F-actin) and myosin-II, this structure generates contractile tension. Actin filaments form a scaffold for myosin-II motor proteins, which slide along them to drive constriction. RhoA plays a central role in activating formin-mediated actin polymerization and myosin-II recruitment. Live-cell imaging has shown that RhoA activity is confined to the cleavage site, ensuring precise deployment of the contractile machinery.
As the ring assembles, it undergoes continuous remodeling. Myosin-II filaments periodically disassemble and reform, regulated by kinases such as ROCK and citron kinase. This turnover maintains contractile force without premature ring disassembly. Cross-linking proteins anillin and septins stabilize actin filaments and the plasma membrane, preventing furrow regression. Studies in Drosophila embryos and mammalian cells show that anillin depletion results in unstable actomyosin networks and cytokinesis failure.
The ring’s organization is refined by scaffolding proteins that tether it to the plasma membrane. Ect2, a guanine nucleotide exchange factor, localizes to the equatorial cortex to facilitate RhoA activation and actin filament assembly. Phosphoinositide lipids within the membrane interact with cytoskeletal regulators to anchor the contractile apparatus. Disruptions in these lipid-protein interactions can misposition the furrow. Research in yeast and vertebrate cells indicates that phosphatidylinositol 4,5-bisphosphate (PIP2) enrichment at the cleavage site enhances actomyosin ring stability, highlighting the role of lipid signaling in cytokinesis.
Membrane Constriction
As the cleavage furrow deepens, the plasma membrane moves inward, leading to the physical separation of the daughter cells. This process integrates mechanical forces with targeted membrane remodeling. The lipid bilayer must remain flexible yet structurally stable to accommodate the narrowing space while maintaining integrity. Phosphoinositide-enriched membrane domains help anchor the cytoskeletal machinery and recruit vesicles that supply additional membrane material.
Vesicular transport sustains membrane remodeling. Endosomal and Golgi-derived vesicles deliver lipids and proteins necessary for furrow ingression, preventing excessive membrane tension. Exocyst complexes, which mediate vesicle tethering, ensure membrane additions occur precisely at the cleavage site. Disruptions in this system can stall constriction or cause membrane rupture, as seen in cells with exocyst component mutations. Dynamin, a GTPase involved in membrane fission, regulates the final stages of constriction by facilitating vesicle scission, ensuring a smooth transition from furrow ingression to abscission.
Differences Across Cell Types
Cleavage furrow formation and constriction vary across cell types, reflecting adaptations to structural and functional needs. In animal cells, furrow ingression is driven by an actomyosin ring, but its rate and mechanics differ depending on cell size, shape, and cortical tension. Large embryonic cells, such as those in Xenopus laevis, undergo rapid furrow ingression to accommodate successive divisions. In contrast, smaller somatic cells constrict more gradually to ensure precise organelle partitioning. Embryonic cells rely on maternal stores of proteins like RhoA and myosin-II, while somatic cells depend on de novo synthesis and localized activation.
Plant cells, which lack a contractile ring due to their rigid cell walls, use a different mechanism. Instead of a cleavage furrow, they form a phragmoplast, composed of microtubules and Golgi-derived vesicles. These vesicles coalesce at the cell center to create a new cell plate, which fuses with the existing wall. Proteins like KNOLLE, a syntaxin involved in membrane docking, coordinate vesicle trafficking and fusion. This reliance on vesicular transport rather than mechanical constriction distinguishes plant cytokinesis from that of animal cells.
Fungal cells, particularly budding yeast (Saccharomyces cerevisiae), exhibit yet another variation. Their cytokinetic machinery includes an actomyosin ring, but a chitin-rich septum reinforces the division site, preventing premature furrow regression. In filamentous fungi like Aspergillus species, septation occurs at regular intervals along hyphae rather than strictly at the cell midpoint, allowing for continuous growth while ensuring proper cytoplasmic partitioning.