Dr. Roshan L. Shrestha, a scientific team member of CHDS-Nepal, along with the teams from Cambridge University and Queen Mary University London, published a paper in Journal of Cell Biology. This was the work that Dr. Shrestha contributed during his doctoral training at Department of Genetics, University of Cambridge, UK under the supervision of Dr. Viji Draviam.
This paper identified the mechanisms that position the mitotic spindle at correct place for proper cell division. This is an important step in cell cycle as defects in cell division may cause tumor development.
The plane of cell division is defined by the final position of the mitotic spindle. The spindle is pulled and rotated to the correct position by cortical dynein. However, it is unclear how the spindle’s rotational center is maintained and what the consequences of an equatorially off centered spindle are in human cells. We analyzed spindle movements in 100s of cells exposed to protein depletions or drug treatments and uncovered a novel role for MARK2 in maintaining the spindle at the cell’s geometric center. Following MARK2 depletion, spindles glide along the cell cortex, leading to a failure in identifying the correct division plane. Surprisingly, spindle off centering in MARK2-depleted cells is not caused by excessive pull by dynein. We show that MARK2 modulates mitotic microtubule growth and length and that codepleting mitotic centromere-associated protein (MCAK), a microtubule destabilizer, rescues spindle off centering in MARK2-depleted cells. Thus, we provide the first insight into a spindle-centering mechanism needed for proper spindle rotation and, in turn, the correct division plane in human cells.
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