# Local PI(4,5)P2 synthesis by septin-associated PIPKIγ isoforms controls centralspindlin association with the midbody during cytokinesis

## TL;DR

The study shows that specific PIPKIγ isoforms work with septins to control midbody organization during cell division by locally producing PI(4,5)P2.

## Contribution

The novel contribution is identifying septin-associated PIPKIγ isoforms as spatiotemporal regulators of midbody formation through local PI(4,5)P2 synthesis.

## Key findings

- Loss of PIPKIγ isoforms disrupts septin and anillin localization at the midbody and intercellular bridge.
- Septins and PIPKIγ isoforms together promote centralspindlin recruitment to the midbody.
- Local PI(4,5)P2 synthesis at the cleavage furrow is essential for midbody organization during cytokinesis.

## Abstract

Cytokinesis critically depends on phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Synthesis of PI(4,5)P2 is crucial for several stages of cytokinesis, including actomyosin ring assembly and constriction, membrane tethering of spindle microtubules, and midbody organization. How these activities of PI(4,5)P2 are spatiotemporally controlled is unknown. Here we unravel a crucial function for local PI(4,5)P2 synthesis at the ingressed cleavage furrow by septin-binding isoforms of PIPKIγ to control midbody formation. We demonstrate that loss of PIPKIγ isoforms perturbs cytokinesis by impairing septin association with microtubules, and anillin and septin deposition at the intercellular bridge and at the midbody. This mechanism requires the ability of PIPKIγ isoforms to synthesize PI(4,5)P2 and to associate with septins. Septins and PIPKIγ further synergize to promote centralspindlin recruitment to the midbody. Our findings establish septin-associated PIPKIγ isoforms as spatiotemporal controllers of midbody organization during cytokinesis that act through generating a local pool of PI4,5P2 at the ingressed cleavage furrow.

Cytokinesis progression depends on the precise regulation of phosphoinositide synthesis. Here, the authors show that septin-associated PIPKIγ isoforms control late midbody organization by local PI(4,5)P2 synthesis at the ingressed cleavage furrow.