Aurora B Kinase Promotes Cytokinesis by Inducing Centralspindlin Oligomers that Associate with the Plasma Membrane

Abstract

SUMMARY In metazoans, cytokinesis is triggered by activation of the GTPase RhoA at the equatorial plasma membrane. ECT-2, the guanine nucleotide exchange factor (GEF) required for RhoA activation, is activated by the centralspindlin complex that concentrates on spindle midzone microtubules. However, these microtubules and the plasma membrane are not generally in apposition, and thus the mechanism by which RhoA is activated at the cell equator remains unknown. Here we report that a regulated pool of membrane-bound, oligomeric centralspindlin stimulates RhoA activation. The membrane-binding C1 domain of CYK-4, a centralspindlin component, promotes furrow initiation in C. elegans embryos and human cells. Membrane localization of centralspindlin oligomers is globally inhibited by PAR-5/14-3-3. This activity is antagonized by the chromosome passenger complex (CPC), resulting in RhoA activation at the nascent cleavage site. Therefore, CPC-directed centralspindlin oligomerization during anaphase induces contractile ring assembly at the membrane.

Central Spindle Self-Organization and Cytokinesis in Artificially Activated Sea Urchin Eggs

“…It is likely that a similar phenomenon is occurring in activated sea urchin eggs. Finally, another recent study showed that a pool of chromosomal passenger complex (CPC)-regulated and membrane-bound centralspindlin can activate RhoA at the ingression site via oligomerization (Basant et al, 2015). This mechanism may help to explain how furrowing can be initiated in activated eggs that lack astral microtubules.…”

Cytokinesis in Metazoa and Fungi

“…This complex localizes prominently to the spindle midzone, which lies at variable distances from the cell membrane, raising the question of how it impacts events on the membrane when they are well separated. Indeed, a second, smaller pool of centralspindlin that localizes to the plasma membrane has recently been shown to play a role (Basant et al 2015). The Cyk4 subunit of centralspindlin contains a weak membranebinding domain (Lekomtsev et al 2012).…”

“…The equatorial localization of centralspindlin is proposed to be under control of the chromosome passenger complex that accumulates at the site of the presumptive furrow (Cooke et al 1987;Basant et al 2015). Aurora B kinase-the catalytic subunit of this complex-promotes centralspindlin oligomerization (Douglas et al 2010).…”

“…During anaphase, centralspindlin undergoes regulated oligomerization. Oligomerization promotes the microtubule association of centralspindlin (Hutterer et al 2009) and membrane localization (Basant et al 2015) through distinct domains. Centralspindlin activates the RhoGEF Ect2, which activates RhoA at the plasma membrane; thus, these interactions could direct positioning of the division plane (Fig.…”

Animal cell cytokinesis: The role of dynamic changes in the plasma membrane proteome and lipidome

“…Given the extraordinary range of functions of the centralspindlin complex, the Glotzer group tested the hypothesis that the membrane binding capacity of this complex described in 2.1 may be important for different facets of its biology [23]. It was already known that centralspindlin hetero-tetramers could assemble into further higher order structures via an oligomerisation signal in MKLP1.…”