Cytokinesis

Cytokinesis is the process whereby the cytoplasm of a single cell is divided to spawn two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two to ensure that chromosome number is maintained from one generation to the next. In animal cells, one notable exception to the normal process of cytokinesis is oogenesis (the creation of an ovum in the ovarian follicle of the ovary), where the ovum takes almost all the cytoplasm and organelles, leaving very little for the resulting polar bodies, which then die. In plant cells, a dividing structure known as the cell plate forms across the centre of the cytoplasm and a new cell wall forms between the two daughter cells.

Animal cell cytokinesis
During normal proliferative divisions, animal cell cytokinesis begins shortly after the onset of sister chromatid separation in the anaphase of mitosis. A contractile ring, comprised of non-muscle myosin II and actin filaments, assembles equatorially (in the middle of the cell) at the cell cortex (adjacent to the cell membrane). Myosin II uses the free energy released when ATP is hydrolysed to move along these actin filaments, constricting the cell membrane to form a cleavage furrow. Continued hydrolysis causes this cleavage furrow to ingress (move inwards), a striking process that is clearly visible down a light microscope. Ingression continues until a so-called midbody structure (composed of electron-dense, proteinaceous material) is formed and the process of abscission then physically cleaves this midbody into two. Abscission depends on septin filaments beneath the cleavage furrow, which provide a structural basis to ensure completion of cytokinesis. After cytokinesis, non-kinetochore microtubules reorganize and disappear into a new cytoskeleton as the cell cycle returns to interphase (see also cell cycle).

Contractile ring positioning
The position at which the contractile ring assembles is dictated by the mitotic spindle. This seems to depend upon the GTPase RhoA, which influences several downstream effectors (such as the protein kinases ROCK and citron) to promote myosin activation (by influencing the phosphorylation of Myosin regulatory light chain (rMLC)) and actin filament assembly (by regulating formin protein) at a particular region of the cell cortex.

The central spindle
Simultaneous with contractile ring assembly during anaphase, a microtubule based structure termed the central spindle (or spindle midzone) forms when non-kinetochore microtubule fibres are bundled between the spindle poles. A number of different species including H. sapiens, D. melanogaster and C. elegans require the central spindle in order to efficiently undergo cytokinesis, although the specific phenotype described when it is absent varies from one species to the next (for example, certain Drosophila cell types are incapable of forming a cleavage furrow without the central spindle, whereas in both C. elegans embryos and human tissue culture cells a cleavage furrow is observed to form and ingress, but then regress before cytokinesis is complete). Seemingly vital for the formation of the central spindle (and therefore efficient cytokinesis) is a heterotetrameric protein complex called centralspindlin. Along with associated factors (such as SPD-1 in C. elegans), centralspindlin plays a role in bundling microtubules to form the spindle midzone during anaphase.

Timing cytokinesis
Cytokinesis must be temporally controlled to ensure that it occurs only after sister chromatid separation during normal proliferative cell divisions. To achieve this, many components of the cytokinesis machinery are highly regulated to ensure that they are able to perform a particular function at only a particular stage of the cell cycle.

Plant cell cytokinesis
Due to the presence of a cell wall, cytokinesis in plant cells is significantly different from that in animal cells. Rather than forming a contractile ring, plant cells construct a cell plate in the middle of the cell. The Golgi apparatus releases vesicles containing cell wall materials. These vesicles fuse at the equatorial plane and form a cell plate. The cell plate begins as a fusion tube network, which then becomes a tubulo-vesicular network (TVN) as more components are added. The TVN develops into a tubular network, which then becomes a fenestrated sheet which adheres to the existing plasma membrane.

Bacterial cell cytokinesis
In bacterial cells, a tubulin-like protein called FtsZ was observed to be distributed equally in the cell, but seen to be forming a ring when cytokinesis takes place. The FtsZ ring becomes narrower by GTP hydrolysis. FtsZ recruits other Fts proteins to the site, among other mureine transpeptidases. It is strongly suggested that the polar regions of a bacterium exclude FtsZ, thereby assuring that the contractile ring forms in the middle of the cell.