Abstract
SummaryCytokinesis, the final step of cell division, begins with the formation of a cleavage furrow. How the mitotic spindle specifies the furrow at the equator in animal cells remains unknown. Current models propose that the concentration of the RhoGEF ECT2 at the spindle midzone and the equatorial plasma membrane directs furrow formation. Using chemical genetic and optogenetic tools, we demonstrate that the association of ECT2 with the plasma membrane during anaphase is required and sufficient for cytokinesis. Local membrane targeting of ECT2 leads to unilateral furrowing, highlighting the importance of local ECT2 activity. ECT2 mutations that prevent centralspindlin binding compromise concentration of ECT2 at the midzone and equatorial membrane but sustain cytokinesis. While the association of ECT2 with the plasma membrane is essential for cytokinesis, our data suggest that ECT2 recruitment to the spindle midzone is insufficient to account for equatorial furrowing and may act redundantly with yet-uncharacterized signals.
Highlights
Cytokinesis is the final step of cell division that partitions sister genomes into the two nascent daughter cells (Morgan, 2006)
To determine whether the association of ECT2 with the membrane is a requirement for cleavage furrow formation in human cells, we employed a chemical genetic system that allowed us to artificially control the association of ECT2 with the plasma membrane
Consistent with other studies (Kim et al, 2005; Wagner and Glotzer, 2016), these results suggest that the N-terminal region of ECT2 that contains the BRCA1 C-terminal (BRCT) repeats and is absent in the guanine nucleotide exchange factor (GEF)-C1B protein might play an important role during cytokinesis
Summary
Cytokinesis is the final step of cell division that partitions sister genomes into the two nascent daughter cells (Morgan, 2006). The cleavage plane needs to be positioned at the cell equator to accurately partition sister genomes and to yield sized progeny (D’Avino et al, 2015; Fededa and Gerlich, 2012; Morgan, 2006). The cleavage plane is specified during anaphase by the mitotic spindle apparatus (Burgess and Chang, 2005; Rappaport, 1996). Two spindle substructures are thought to position the cytokinetic furrow at the equatorial cortex: astral microtubules and the spindle midzone, a structure formed by antiparallel microtubules between segregating sister genomes in anaphase (Bringmann and Hyman, 2005; Dechant and Glotzer, 2003). How the mitotic spindle breaks cortical isotropy to generate an equatorial contractile zone and thereby positions the cleavage plane is one of the major unresolved questions in cell biology
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