18.14: The Contractile Ring

Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.

A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes actin filament formation, whereas the activation of multiple protein kinases by RhoA stimulates the myosin II assembly and contraction. The kinases phosphorylate the myosin light chain and stimulate filament formation and motor activity. In addition to actin and myosin II (actomyosin), septin filaments are also involved in contractile ring formation. Septin filaments stabilize the contractile ring and play an important role in yeast cytokinesis.

The activation of RhoA is regulated by a guanine nucleotide exchange factor (Rho-GEF). This protein is found in the cortex region, which is the site of future cell division. The inactive form of RhoA is bound to GDP. Rho-GEF exchanges the GDP bound to RhoA with GTP. The binding of GTP activates RhoA, which in turn triggers the formation of contractile rings.

RhoA also regulates the activity of the scaffold protein anillin, an essential player in contractile ring formation. While RhoA is considered the principal activator for the assembly of the contractile ring, anillin acts as the main organizer for the ring by binding with actin, myosin II, membrane phospholipids, septin, and other structural and regulatory components involved in contractile ring formation.

The continuous shrinkage of the contractile ring means it progressively needs a smaller number of actomyosin filaments to form a ring of the same thickness; therefore, concomitant disassembly of the actomyosin filaments occurs as the ring contracts. During the final stages of the cytokinesis, the contractile ring and the central spindle containing compact microtubules matures to form the midbody and the midbody ring. The midbody ring then carries out the abscission of the parent cell, resulting in the formation of two daughter cells.

The final step of the cell cycle that divides a cell into two daughter cells is called cytokinesis. Cytokinesis begins after chromosome separation in mitosis and ends when the cell divides.

The beginning of cytokinesis is marked by the appearance of a crease, called the cleavage furrow. Starting in anaphase, the furrow deepens and spreads to form a ring around the cell. This compression, which ultimately divides the cell into two, is generated by the contractile ring.

A protein called RhoA is the chief regulator of contractile ring assembly and function. To ensure the contractile ring is formed in the right place, RhoA is activated locally at the cell cortex, near the equator of the cell. RhoA, along with anaphase spindle fibers, also ensures that the contractile ring is formed at the right time, after chromosome segregation.

The contractile ring is made up of structural proteins, including actin filaments and myosin II filaments. RhoA activity results in the assembly of myosin II and anti-parallel actin filaments into the structure of the contractile ring. RhoA promotes localized actin filament polymerization which is necessary for the contractile ring formation.

The contractile ring components generate the force necessary to divide the cell. One mechanism of contraction involves myosin motor activity. Here, myosin filaments move toward the plus end of adjacent antiparallel actin filaments.  This activity pulls the anti-parallel actin, causing them to slide past one another, contracting the ring.

The contraction of the ring continues until it pinches off two new cells. The ring is degraded once the new cells are formed.

Inefficient or absence of contractile ring formation can lead to abnormal cell division, impaired growth, and the potential for tumor formation.