Cell division is a relatively familiar concept for everyone since it is one of the recurring topics in biology -- mitosis and meiosis, and all. Cell division is important for the reproduction, and repair of the tissues and over-all growth of the organism. However, rapid cell division leads to the formation of tumors which, most of than not, leads to cancer. Recently, a team of researchers from Princeton University successfully recreated an important process in cell division in a test tube. This experiment helped them uncover the vital role of a protein that is elevated in over 25% of all cancers.
The findings, which are published in Nature Communications, describes a key step towards the recreation of the entire cell division machinery that can lead to new therapies with the primary goal of preventing the growth of cancer cells. Usually, when cells undergo division, the microtubules (those spindle-shaped structures composed of thousand of filaments) attaches itself to the chromosomes then pulls each chromosome into each newly-forming cell. Each of these microtubules is assembled from tubulin molecules and because the chromosomes must assemble intro these microtubules at the right moment, an error in segregation can lead to cancer. To be able to complete this process correctly, another process called branching microtubule nucleation is necessary. The branching microtubule nucleation is crucial because it allows the cells to form a huge amount of microtubules enabling the capture of the chromosomes.
READ: Laser Can Detect Cancer Cells and Kill It
The crucial process of the branching microtubule nucleation is depending largely on several pieces of "molecular machinery". For instance, the gamma-tubulin ring complex is the one responsible for initiating the assembly of tubulin molecules into microtubules. Meanwhile, the augmin complex is the one responsible for engaging the gamma-tubulin ring complex to the existing microtubules. The Targeting Protein for Xklp2 or TPX2 is also involved in this process, however, researchers identified that this is protein is elevated in over 25% in all forms of cancer.
The elevated TPX2 levels can lead to the abnormal assembly of microtubules in cells. Sabine Petry, an assistant professor of molecular biology, explains that to be able to better understand branching microtubule nucleation, the researchers had to do the process outside of the cell using putrified proteins. The researchers found out that like the augmin complex, TPX2 can bind microtubules and recruit gamma-tubulin ring complex to initiate the process of branching microtubule nucleation. They were also surprised to discover that TPX2 is also responsible for recruiting augmin to microtubules.
According to graduate student Raymundo Alfaro-Aco, the process of branching microtubule nucleation occurs most efficiently when the three molecular pieces are all present. "Surprisingly, TPX2 is at the heart of controlling this process even though it is a single protein." He said. In the published paper, Petry and her graduate student Matthew King further explains that TPX2 forms a liquid layer on the surface of existing microtubules to promote branching microtubule nucleation. These liquid layers will bead up into droplets containing tubulin. The team was also able to discover that TPX2 and tubulin can condense together to form droplets through a phase-separation mechanism (kind of similar to the mechanism that makes oil droplets form in water).
A new batch of microtubules can be formed from these droplets and can result in the formation of branched microtubule structures by condensing on the surface of the existing microtubules. King explains that the condensation of TPX2 and tubulin creates a reservoir of tubulin in a pre-existing microtubule. "It may be necessary to efficiently promote the process of branching microtubule nucleation." He said.
