An anillin-CIN85-SEPT9 complex promotes intercellular bridge maturation required for successful cytokinesis.

Cleavage of one cell into two is the most dramatic event in the life of a cell. Plasma membrane fission occurs within a narrow intercellular bridge (ICB) between the daughter cells, but the mechanisms underlying ICB formation and maturation are poorly understood. Here we identify CIN85 as an ICB assembly factor and demonstrate its requirement for robust and timely cytokinesis. CIN85 interacts directly with the N-terminal region of anillin and SEPT9 and thereby facilitates SEPT9-containing filament localization to the plasma membrane of the ICB. In contrast, the C-terminal pleckstrin homology (PH) domain of anillin binds to septin units lacking SEPT9 but enriched in SEPT11. Anillin's interactions with distinct septin units are required to promote ICB elongation and maturation that, we propose, generate the physical space into which the abscission machinery is recruited to drive the final membrane scission event releasing two independent daughter cells.

Inhibition of polar actin assembly by astral microtubules is required for cytokinesis.

During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a ß-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the ß- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies ß-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1. During anaphase, CLIP170 is delivered by astral microtubules and displaces IQGAP1 from DIAPH1, leading to formin autoinhibition, a decrease in cortical stiffness and localized membrane blebbing. The contemporaneous production of a ß-actin contractile ring at the cell equator and loss of γ-actin from the poles is required to generate a stable cytokinetic furrow and for the completion of cell division.