Cell biology: Strategy of Dis1 protein for microtubule shortening in fission yeast

Recently, a team of researchers including Professor Masamitsu Sato and Ph.D student Yuichi Murase from the Department of Life Science and Medical Bioscience at Waseda University, Mika Toya from the Global Center of Science and Engineering at Waseda University, Junichiro Yajima from the Department of Life Sciences at the University of Tokyo, and Takahiro Hamada from the Department of Bioscience, Okayama University of Science conducted a study to identify these non-kinesin proteins.

It is known that proteins from the TOG/XMAP215 family such as Dis1 are involved in microtubule elongation in certain species. However, previous findings have indicated that even in cells without the Dis1 protein, the length of the microtubules is similar to that of normal cells. Elaborating further, Sato says, "Twenty years back, researchers considered TOG proteins as conventional microtubule stabilizers and believed that kinesin is the only factor responsible for microtubule shortening to carry chromosomes. But my observation through a microscope indicated that Dis1 acted like a de-stabilizer, making me curious about how exactly microtubule shortening occurs in yeast."

In this study, which was published online on November 26, 2022, in Communications Biology, the team tested their hypothesis that Dis1 might be involved in microtubule shortening in yeast.

To arrive at their findings, the team conducted in vitro and in vivo experiments in yeast cells. They captured images of microtubules in yeast via fluorescence microscopy and examined how Dis1 modified microtubule length. Images captured within intervals of five seconds depicted that Dis1 promotes microtubule shortening through microtubule catastrophe -- a process in which growing microtubules suddenly switch into a rapidly shortening state.

Before being split and pulled, chromosomes are held in place by microtubules emanating from the opposite poles. The team observed that Dis1 collects near the tip of the microtubule at the point in the chromosome where microtubules attach, known as the kinetochore. This suggests that Dis1 causes microtubule catastrophe by remaining anchored to the microtubule-kinetochore junction, thereby causing a sudden shortening of microtubules.

To test whether Dis1 is indeed involved in chromosome pulling, the team created artificial Dis1 oligomers which were then tethered to the chromosome arm region, to induce artificial chromosome pulling in yeast. The team observed smooth and frequent pulling of chromosomal arms by the microtubules connected to the artificial Dis1 kinetochore towards the spindle poles.

The interaction of Dis1 with the microtubules in fission yeast is unique and unexpected since TOG/XMAP215 proteins are known to be involved in microtubule polymerization, the process that leads to microtubule elongation in many organisms.

What are the long-term applications of these findings? Sato muses, "We envision that the molecular device created in this study can be a platform for the artificial chromosome segregation machinery, which might contribute to therapy for diseases that are caused by defects in chromosome segregation. Alternatively, it could be used for the construction of artificial cells that can segregate genetic materials to descendants independently."