User:Midbody/sandbox

The midbody is a transient organelle that bridges two daughter cells just prior to abscission. The midbody is structurally composed of microtubules derived from the mitotic spindle which compact during the final stages of cell division. Aside from microtubules, the midbody also contains various proteins that are involved in cytokinesis, asymmetric cell division, and chromosome segregation. The midbody is important for completing the final stages of cytokinesis and abscission. The precise role in these processes is not yet clearly defined as the midbody is still an active area of research and discovery.

Discovery
The midbody was first observed by Walther Flemming in 1891. Flemming described the midbody (which is often referred to as the ‘Flemming Body’) as a structural remnant of cytokinesis. Cytokinesis is the cytoplasmic division of a cell into two daughter cells at the end of mitosis or meiosis. For some time scientists considered the midbody to be nothing more than structural waste remaining after cytokinesis. In 2004, Skop et al. showed that the midbody was not merely a useless remnant, but that it had functions important for spindle alignment and cell division. Her research, which was published in Nature, changed the way people understood the midbody; it was now considered to be a functional organelle.

Structure
The midbody is a complex of condensed microtubules derived from the spindle midzone. Generally, the midbody is found to have a diameter of 1 micrometer and a length of 3 to 5 micrometers .). Formed by the cleavage furrow during cytokinesis, the midbody is also composed of a variety of proteins which have active involvement in the abscission process. Over 160 proteins were found to be associated with the midbody which were organized into 5 main categories according to their function . The largest group of proteins had secretory and other membrane associated functions. The other groups of proteins involved had actin associated functions, microtubule associated functions and kinase activity in order of decreasing proportion.

Structural Zones
The midbody has three well defined zones; the central bulge, the central dark zone, and the flanking zone. When furrow ingression takes place during cytokinesis, the cleavage furrow anchors to the central bulge. The central bulge contains very few microtubules and is composed of various proteins including centralspindlin. Centralspindlin rearranges in a small, dense, cortically associated ring surrounding the midbody. This protein ring acts as an anchor for midbody associated proteins that play a role in abscission. In the central dark zone, antiparallel microtubules overlap, functioning as the structural architecture of the midzone. The passenger protein Aurora B acts as a marker for abscission to begin by binding to the flanking zone.

Formation
The midbody structure forms in the intracellular bridge connecting the two daughter cells and creates an observable electron dense band near the middle that is approximately 800-900 nm in thickness. The midbody is formed by the interdigitation of aster microtubules that are antiparallel, meaning the microtubules on opposite side of the spindle equator have opposite polarities. The polarity of these microtubules is essential for the proper formation of the structure, development, and function of the midbody. Cep55 has proven to be important for the proper formation and function of the midbody, as Cep55 knock-out cells have either no midbody formation, or midbodies that are in the wrong location and have misplaced structural and regulatory components.

Function
The main function of the midbody is to control abscission. Abscission is the final separation of the two daughter cells and can only occur after the chromosomes have segregated, the cleavage furrow has formed, and the cell has contracted. This process is therefore tightly regulated to ensure that abscission happens at the correct time.

Role in Cytokinesis
Polio-like kinase 1 (Plk1) is a protein that has two main functions during cytokinesis; it triggers the formation of the cleavage furrow and also phosphorylates a protein called Cep55. The phosphorylation of Cep55, an abscission-promoting factor, by Plk1 prevents early recruitment to the midbody. It has been shown that when Cep55 cannot be phosphorylated (due to a mutation at its phosphorylation site) the recruitment of Cep55 occurs too early and abscission does not happen. When Plk1 is inhibited, premature recruitment of Cep55 and lack of abscission are observed. Plk1 must be degraded before Cep55 can be recruited to the midbody because when its degradation is prevented, the level of Plk1 in the cell continues to increase and Cep55 is never recruited. Therefore Cep55 is negatively regulated by Plk1 to ensure timely recruitment to the midbody and abscission of the cell.

It has also been suggested that the midbody functions to stabilize the intracellular bridge connecting the daughter cells after the disappearance of the contractile ring. Cells that fail to divide can later merge together but only after the midbody in the intracellular bridge has degraded, implying the midbody is responsible for bridge stabilization. The midbody may act as a glue that binds the midbody microtubules to the plasma membrane of the cleavage furrow.

Spindle Positioning
Spindle positioning is an important event required for the formation of cells that are unequal in size during cell division as well as for the determination of the cleavage plane geometry. The asymmetric formation of daughter cells provides a positional cue for later cell division where it is used as a marker for astral microtubule mediated spindle orientation.

Membrane remodelling and vesicular trafficking proteins endophilin B1, HIP1/DUO, Copine I, and CLIP-170 were identified as proteins required for proper spindle rotation by providing cortical cues or through promoting interactions between the plasma membrane and the various astral microtubules. These spindle rotation associated proteins were identified in the midbody suggesting that the midbody has an important functional role in spindle positioning.

Abscission in Plant Cells
While the midbody plays an important role in cytokinesis and abscission in animal cells, in plant cells abscission occurs through the formation of a new cell wall between the two daughter cells. This occurs through fusion of the predominantly golgi-derived vesicles which form the phragmoplast at the plane of cell division ). The phragmoplast acts as scaffold for cell plate assembly allowing for the subsequent formation of a new cell wall . In animal cells the golgi stacks normally undergo fragmentation during mitosis such that the organelle is shared between the two daughter cells . The midbody functions similarly to the phragmoplast and similarly it contains golgi-associated components required for cytokinesis suggesting that similar evolution of these structures.