Mechanochemical crosstalk produces cell-intrinsic patterning of the cortex to orient the mitotic spindle

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Abstract

Proliferating animal cells are able to orient their mitotic spindles along their interphase cell axis, setting up theaxis of cell division, despite rounding up as they enter mitosis. This has previously been attributed to molecular memory and, more specifically, to the maintenance of adhesions and retraction fibers in mitosis [1–6],which are thought to act as local cues that pattern cortical Gai, LGN, and nuclear mitotic apparatus protein (NuMA) [3, 7–18]. This cortical machinery then recruits and activates Dynein motors, which pull on astral microtubules to position the mitotic spindle. Here, we reveal a dynamic two-way crosstalk between the spindle and cortical motorcomplexes that depends on a Ran-guanosine triphosphate (GTP) signal [12], which is sufficient to drive contin-uous monopolar spindle motion independently of adhesive cues in flattened human cells in culture. Building onprevious work [1, 12, 19–23], we implemented a physical model of the system that recapitulates the observed spindle-cortex interactions. Strikingly, when this model was used to study spindle dynamics in cells entering mitosis, the chromatin-based signal was found to preferentially clear force generators from the short cell axis, so that cortical motors pulling on astral microtubules align bipolar spindles with the interphase long cell axis, without requiring a fixed cue or a physical memory of interphase shape. Thus, our analysis shows that the ability of chromatin to pattern the cortex during the process of mitotic rounding is sufficient to translate inter-phase shape into a cortical pattern that can be read by the spindle, which then guides the axis of cell division.

Journal details

Journal Current Biology
Pages Epub ahead of print
Available online
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