TY - JOUR
T1 - Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism
AU - Zulkipli, Ihsan
AU - Clark, Joanna
AU - Hart, Madeleine
AU - Shrestha, Roshan L.
AU - Gul, Parveen
AU - Dang, David
AU - Kasichiwin, Tami
AU - Kujawiak, Izabela
AU - Sastry, Nishanth
AU - Draviam, Viji M.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054637969&partnerID=8YFLogxK
U2 - 10.1083/jcb.201804166
DO - 10.1083/jcb.201804166
M3 - Article
AN - SCOPUS:85054637969
SN - 0021-9525
VL - 217
SP - 3057
EP - 3070
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 9
ER -
