# Actin Cytoskeleton Network Self-Organization

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $409,363

## Abstract

PROJECT ABSTRACT/SUMMARY
 Cells assemble functionally diverse actin cytoskeleton networks with distinct architectures and
dynamics to drive fundamental processes such as polarization, endocytosis, motility and division. The
specific characteristics of different actin filament networks (actin filament density, organization and
dynamics) are determined through the coordination action of specific sets of actin binding proteins
(ABPs) with complementary binding properties. Most investigations primarily focus on individual F-actin
networks. However, this provides limited overall understanding of F-actin network organization and
function because cells typically assemble and use multiple F-actin networks simultaneously within the
same cytoplasm. Consequently, F-actin networks must self-organize from a common pool of shared
actin monomers and overlapping sets of ABPs. We have predicted that there are important interactions
(cross talk) between networks that are critical for their form and function. Our long-term goal is to
discover the direct and indirect interactions between self-organized F-actin networks, which are critical
for establishing their unique identities and functions within a common cytoplasm, and to determine the
underlying molecular mechanistic principles that govern these interactions.
 We are investigating two major actin cytoskeleton self-organization questions. The first is to
determine the mechanisms by which the size and density of F-actin networks are regulated by
competition for a limiting amount of actin monomers (Aim I). Although unassembled G-actin was not
thought to be limiting, we systematically showed that competition for G-actin helps control the size and
density of competitive F-actin networks in fission yeast, and that the actin monomer protein profilin plays
a major role in regulating competition for limiting G-actin. Our goal is to determine the underlying
mechanism by which profilin and other ABPs contribute to the proper distribution of G-actin between
functionally diverse actin cytoskeleton networks. The second is to determine how diverse F-actin
networks acquire the specific set of ABPs whose complementary biochemical activities help define their
form and function (Aim II). We will investigate the underlying intrinsic molecular mechanisms by which
ABPs self-sort to particular F-actin networks within a common cytoplasm, including (1) the contribution of
competition and cooperation between ABPs for associating with actin filaments, and (2) whether actin
assembly factors initiate self-sorting by biasing the association of particular ABPs.

## Key facts

- **NIH application ID:** 10543764
- **Project number:** 5R01GM079265-13
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** David R Kovar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $409,363
- **Award type:** 5
- **Project period:** 2007-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543764

## Citation

> US National Institutes of Health, RePORTER application 10543764, Actin Cytoskeleton Network Self-Organization (5R01GM079265-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10543764. Licensed CC0.

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