Actin and Myosin II in the Contractile Ring Generate the Force for Cytokinesis

As the astral microtubules in anaphase become longer lived and less dynamic in response to the loss of M-Cdk activity, the contractile ring begins to assemble beneath the plasma membrane. Much of the preparation for cytokinesis, however, happens earlier in mitosis, before the division of the cytoplasm actually begins. In interphase cells, actin and myosin filaments are assembled into a cortical network and, in some cells, also into large cytoplasmic bundles called stress fibers (discussed in Chapter 16). As cells enter mitosis, these arrays disassemble; much of the actin is reorganized, and myosin II filaments are released. As the chromatids separate in anaphase, myosin II begins to accumulate in the rapidly assembling contractile ring (Figure 18-34).

In many cells, cytokinesis requires the activation of one or more members of the polo-like family of protein kinases. These kinases regulate the assembly of both the mitotic spindle and the contractile ring and are therefore thought to help coordinate mitosis and cytokinesis, but it is uncertain how they do so. The fully assembled contractile ring contains many proteins in addition to actin and myosin II. The overlapping arrays of actin filaments and bipolar myosin II filaments, however, generate the force that divides the cytoplasm in two. They are thought to contract by a mechanism that is biochemically similar to that used by smooth muscle cells; in both cases, for example, the contraction begins when Ca2+-calmodulin activates myosin light-chain kinase to phosphorylate myosin II. Once contraction has been stimulated, the ring develops a force large enough to bend a fine glass needle that is inserted in the path of the constricting ring.

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How the contractile ring constricts is still a mystery. It seems not to operate by a simple “purse-string” mechanism, with actin and myosin II filaments sliding past each other as in skeletal muscle (see Figure 16-71). As the ring constricts, the ring maintains the same thickness in cross-section, suggesting that its total volume and the number of filaments it contains decrease steadily. Moreover, unlike in muscle, the actin filaments in the ring are highly dynamic, and their arrangement changes extensively during cytokinesis.

In addition to specifying the site of contractile ring assembly in early anaphase, in many cells, microtubules also work continuously during anaphase and telophase to stabilize the advancing cleavage furrow. Drugs that depolymerize microtubules, for example, cause the actin filaments in the contractile ring to become less organized. Moreover, if a needle is used to tear microtubules away from the cell cortex, the contractile ring disassembles and the cleavage furrow regresses. It is not known how the microtubules stabilize the ring, although it has been shown that growing microtubules can activate some members of the Rho family of small GTPases, which in turn stimulate actin polymerization (discussed in Chapter 16). One member of this family, Rho A, is required for cytokinesis.

The contractile ring is finally dispensed with altogether when cleavage ends, as the plasma membrane of the cleavage furrow narrows to form the midbody. The midbody persists as a tether between the two daughter cells and contains the remains of the central spindle, which now consists of the two sets of antiparallel overlap microtubules packed tightly together within a dense matrix material (Figure 18-35). Remarkably, in some cells, before cytokinesis has been completed, the mother centriole from one or both daughter cells separates from its daughter centriole (see Figure 18-5c) and migrates into the midbody, where it lingers for minutes, before returning to its daughter cell. Only then do the two daughter cells separate to complete cytokinesis. What the centriole might do in the midbody to trigger the final steps of cytokinesis is not known. After the daughter cells separate completely, some of the components of the residual midbody often remain on the inside of the plasma membrane of each cell, where they may serve as a mark on the cortex that helps to orient the spindle in the subsequent cell division.