# Geometry-dependent assembly of the septin cytoskeleton

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $296,757

## Abstract

Summary/abstract Cell shape is integral to function and can be described in terms of plasma
membrane curvature. Many changes in cell curvature occur on the micrometer scale but
proteins are nanometers in size, raising the question as to how cells can perceive, control and
use micrometer-scale geometry. The septins are a conserved, filament-forming family of
proteins that preferentially assemble at sites of micrometer-scale membrane curvature. Septins
assemble on many curved surfaces including at the cytokinetic furrow, dendritic spines,
membrane blebs, around intracellular bacteria and bases of cilia and flagella. Given these
diverse cell contexts, malfunction of septins is linked to diverse human diseases including
many cancers, neuropathies and infertility. At sites of micrometer-scale membrane curvature,
septins can influence the diffusion of proteins in the membrane, act as scaffolds to bring
together signaling proteins, and impact the rigidity of the cell cortex. How curved septin
assemblies form and recruit signaling proteins to the local membrane is critical to understand
how septins link cell geometry to responses. Septin filament assembly occurs through
annealing of short (~24-32nm) oligomeric rods on lipid bilayers or other cytoskeletal networks.
We hypothesize that cells modulate the membrane affinity, length, density, and geometrical
arrangement of septins in a curvature-dependent manner. The goal of this proposal is to
identify the mechanisms directing assembly of septins on curved surfaces and to measure how
curved assemblies regulate signaling networks. We will combine a variety of imaging
approaches including high-resolution fluorescence, SEM and high-speed atomic force
microscopy (HS-AFM), modeling, proteomics, and molecular genetics. Based on preliminary
data, we hypothesize that curvature-dependent septin assembly involves mechanisms at work
on several length scales. This work will be directed by three aims: (1) Analyze septin
membrane interaction in curvature sensing; (2) Determine the biophysical properties of septin
filaments that enable curvature sensing; (3) Identify how curved septin assemblies recruit
specific signaling proteins. From the proposed experiments, we will learn how nanometer
length scale mechanisms contribute to the emergent mesoscale process of sensing micron-
scale curvature. These studies will also reveal how septin scaffolding may change as a
function of local curvature. The long-term goal of this proposed study is to identify how
septins recognize micrometer-scale curvature and then use shape information to modulate
cellular functions.

## Key facts

- **NIH application ID:** 10150863
- **Project number:** 5R01GM130934-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Amy S Gladfelter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $296,757
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150863

## Citation

> US National Institutes of Health, RePORTER application 10150863, Geometry-dependent assembly of the septin cytoskeleton (5R01GM130934-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10150863. Licensed CC0.

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