Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism

Ihsan Zulkipli, Joanna Clark, Madeleine Hart, Roshan L. Shrestha, Parveen Gul, David Dang, Tami Kasichiwin, Izabela Kujawiak, Nishanth Sastry, Viji M. Draviam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3057-3070
Number of pages14
JournalJournal of Cell Biology
Volume217
Issue number9
Early online date25 Jun 2018
DOIs
Publication statusPublished - 1 Sept 2018

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