# The origin of septin ring size control in budding yeast

## TL;DR

This study explores how budding yeast control the size of septin rings, which scale with cell size, by combining experiments and modeling.

## Contribution

The study reveals that positive feedback in Cdc42 polarization and increased polarity proteins with cell growth explain septin ring size scaling.

## Key findings

- Positive feedback in Cdc42 polarization and increased polarity proteins with cell size explain septin ring scaling.
- Disruption of Bni1 leads to diffuse exocytosis and abnormally large septin rings.
- Disruption of Cdc24-dependent feedback increases Cdc42 cluster area but not septin ring size.

## Abstract

The size of organelles and cellular structures needs to be tightly regulated and coordinated with overall cell size. A well-studied example is the Cdc42-driven polarization and subsequent septin ring formation in Saccharomyces cerevisiae, where the size of the resulting structures scales with cell size. However, the mechanisms underlying this scaling remain unclear. Here, we combine live-cell imaging, genetic perturbations, and three-dimensional mathematical modeling to investigate how septin ring size is controlled. Our integrative approach reveals that positive feedback in the polarization pathway, together with an increase of the amount of polarity proteins as cell size grows, can explain the scaling of the Cdc42 cluster and, consequently, septin ring diameter. Additionally, we show that in cells lacking the formin Bni1, where F-actin-cable assembly and directed polarization are disrupted, exocytosis becomes diffuse, leading to abnormally large septin rings. By integrating new experimental findings and mathematical modeling of yeast polarization, our study provides insights into the origin of septin ring size control.

Cdc42-driven polarization and subsequent septin ring formation in S. cerevisiae is a prominent example for formation of a subcellular structure that scales with cell size. This study integrates new experimental findings, Cdc42 polarization modelling, and a mechanistic model of septin ring assembly to provide insight into the mechanisms of septin-ring size control.

Positive feedback in the Cdc42 polarization pathway and an increase in the amount of polarity proteins with cell size growth explains the scaling of the Cdc42 cluster and septin ring diameter.In cells lacking formin Bni1, F-actin cable assembly and directed polarization are disrupted, resulting in diffused exocytosis and abnormally large septin rings.Disruption of Cdc24-dependent negative feedback in the polarization pathway increases the Cdc42 cluster area but leaves septin ring diameter largely unaffected.

Positive feedback in the Cdc42 polarization pathway and an increase in the amount of polarity proteins with cell size growth explains the scaling of the Cdc42 cluster and septin ring diameter.

In cells lacking formin Bni1, F-actin cable assembly and directed polarization are disrupted, resulting in diffused exocytosis and abnormally large septin rings.

Disruption of Cdc24-dependent negative feedback in the polarization pathway increases the Cdc42 cluster area but leaves septin ring diameter largely unaffected.

Positive feedback in the Cdc42 polarization pathway and cell growth-associated increase in the levels of septin-recruiting proteins explains the scaling of the septin ring with cell size.