Cytokinesis in Animal Cells: Mechanisms and Steps

Cell division ensures the proper distribution of genetic material and cellular components into daughter cells. In animal cells, cytokinesis is the final step, physically separating one cell into two. This process requires coordination of cytoskeletal elements, signaling pathways, and membrane remodeling.

A series of regulated events drive cytokinesis, including contractile ring formation, membrane ingression, midbody assembly, and abscission. Each step must be executed precisely to maintain genomic stability and prevent errors that could lead to developmental defects or disease.

Contractile Ring Dynamics

The contractile ring, an actomyosin-based structure, drives the separation of daughter cells. Its formation begins in late anaphase when a cortical band of actin filaments and myosin-II assembles at the equatorial plane. Anchored to the plasma membrane, it undergoes remodeling to generate the forces necessary for furrow ingression. Signals from the mitotic spindle, particularly central spindle and astral microtubules, define the division plane. Disruptions in this regulation can lead to asymmetric division or cytokinesis failure, affecting cell fate and tissue organization.

Once assembled, the ring constricts through myosin-II motor activity, pulling the membrane inward. Actin filament turnover, regulated by cofilin and profilin, ensures adaptability to mechanical stresses. Crosslinking proteins like anillin stabilize the ring by linking it to the plasma membrane and cytoskeletal components. A balance between actin polymerization and depolymerization is essential—excessive stabilization impedes constriction, while excessive turnover causes premature disassembly.

The contractile ring continuously recruits and releases proteins. Septins form a scaffold supporting the ring, while formins promote actin filament elongation. Phosphorylation by kinases such as Aurora B and Rho-associated kinase (ROCK) modulates myosin-II activity and actin organization. These regulatory mechanisms maintain a controlled constriction rate, preventing mechanical failure or incomplete division.

Rho GTPases and Regulatory Proteins

Rho GTPases regulate cytokinesis by controlling cytoskeletal dynamics. RhoA plays a key role by coordinating actomyosin ring assembly and contraction. Its activation at the equatorial cortex is controlled by guanine nucleotide exchange factors (GEFs) like ECT2, which facilitate GDP-GTP exchange. Activated RhoA recruits effectors such as ROCK and diaphanous-related formins (mDia), which regulate actin organization and myosin-II activity. Spatial and temporal regulation of RhoA ensures contractile forces are generated at the correct location, preventing division errors.

RhoA activity is counterbalanced by GTPase-activating proteins (GAPs) like MgcRacGAP, which promote GTP hydrolysis to return RhoA to its inactive state. Scaffolding proteins like anillin stabilize active RhoA at the cleavage site by linking it to actin and myosin-II. Disruptions in RhoA signaling, whether due to mutations or mislocalized activity, can cause cytokinetic defects such as multinucleation or failed abscission, contributing to tumorigenesis and developmental disorders.

Other Rho family GTPases, including Rac1 and Cdc42, regulate distinct aspects of cytoskeletal remodeling. Rac1 influences cortical tension, while Cdc42 regulates septin localization, supporting contractile ring stability. Their coordinated activity ensures mechanical and spatial precision during cytokinesis, minimizing division errors.

Membrane Ingression and Vesicle Trafficking

As actomyosin-driven forces pull the plasma membrane inward, lipid bilayer remodeling accommodates changes in cell shape. Membrane ingression relies on targeted vesicle delivery to prevent excessive tension that could lead to rupture. Intracellular trafficking pathways direct vesicles carrying membrane components and regulatory proteins to the cleavage furrow.

Endocytic recycling repurposes membrane material from other regions of the cell. Clathrin-mediated endocytosis and Rab11-positive recycling endosomes ensure a steady supply of phospholipids and membrane-associated proteins. Disruption of Rab11 impairs furrow ingression and cytokinesis. The exocyst complex tethers vesicles to the plasma membrane, facilitating targeted fusion at the cleavage site.

Phosphoinositide signaling regulates vesicle trafficking and membrane deformation. Phosphatidylinositol 4,5-bisphosphate (PIP2) accumulates at the cleavage furrow, recruiting proteins involved in membrane curvature and actin remodeling. Dynamin, a GTPase, mediates vesicle scission, ensuring membrane remodeling remains dynamic and responsive to furrow constriction.

Midbody Assembly

As cytokinesis progresses, the intracellular bridge between daughter cells forms a protein-rich structure called the midbody. This transient organelle coordinates the final steps of division. It consists of bundled microtubules, scaffold proteins, and signaling molecules that recruit factors necessary for abscission. Microtubule-associated proteins such as PRC1 crosslink antiparallel microtubules, while MKLP1, a kinesin motor protein, facilitates midbody organization.

The midbody composition is dynamic, with proteins being selectively enriched or degraded. The centraspindlin complex, containing MKLP1 and MgcRacGAP, stabilizes the midbody and recruits downstream effectors. Aurora B kinase modulates protein localization and activity, ensuring midbody functionality. ESCRT-III components, known for their role in membrane remodeling, facilitate scission of the remaining membrane tether.

Cytokinetic Abscission

The final step, abscission, physically separates daughter cells. This process requires precise regulation of membrane scission, cytoskeletal disassembly, and protein trafficking. Checkpoint mechanisms delay membrane severing until chromatin and cytoplasmic components are properly segregated, preventing division errors that could lead to binucleation or chromosomal instability.

The ESCRT machinery drives membrane scission at the midbody. ESCRT-III assembles into helical filaments that constrict the intercellular bridge, leading to membrane fission. The ATPase VPS4 remodels and disassembles ESCRT-III structures, completing abscission. Phosphoinositide signaling, particularly PI(3)P-enriched domains at the midbody, guides ESCRT protein recruitment, ensuring severing occurs at the optimal location.