# Coordination of multiple ADF-H family proteins in controlling actin cytoskeleton dynamics

> **NIH NIH F31** · BRANDEIS UNIVERSITY · 2021 · $32,063

## Abstract

Project Summary
The goal of this proposal is to understand how two different members of the Actin Depolymerizing Factor
Homology (ADF-H) family of actin-regulatory proteins, Cofilin and Abp1, influence each other’s interactions with
and functional effects on actin. Cofilin and Abp1 are highly abundant and ubiquitous in vivo, and they both bind
directly to actin filaments using structurally related ADF-H domains, yet these two proteins have strikingly
different effects on actin filament dynamics. Cofilin promotes severing, depolymerization, and debranching of
filaments, whereas Abp1 instead promotes assembly of filaments by Arp2/3 complex and protects (rather than
destabilizes) filament branch junctions. This raises a key question: how do Cofilin and Abp1 co-exist on the same
filamentous actin structures in cells, and how do they affect each other’s functions at these locations? Based on
preliminary data that I have gathered, my working hypothesis is that cells express a level of Abp1 that allows it
to carry out its functions in promoting actin assembly without interfering with Cofilin’s functions in actin
disassembly. Further, I hypothesize that this balance is achieved in part because of key differences in the binding
kinetics of Cofilin and Abp1 on actin filaments. However, my preliminary data also suggest that the same
physiological concentrations of Abp1 strongly interfere with Cofilin-mediated debranching of filaments. I
hypothesize that this is because Abp1 stably binds to branch junctions and competitively blocks Cofilin binding
to Arp2/3 complex. To test these models, I will use an integrated approach combining biochemistry and in vitro
single molecule imaging with genetics and live-cell imaging in S. cerevisiae. The aims of the proposal are: (1) In
vitro analysis of Abp1 effects on Cof1-mediated actin disassembly and debranching, and (2) In vivo
analysis of the relationship between Abp1 and Cofilin in regulating actin dynamics.

## Key facts

- **NIH application ID:** 10212353
- **Project number:** 5F31GM139334-02
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Reynaldo Aguilar Lopez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,063
- **Award type:** 5
- **Project period:** 2020-07-16 → 2022-07-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212353

## Citation

> US National Institutes of Health, RePORTER application 10212353, Coordination of multiple ADF-H family proteins in controlling actin cytoskeleton dynamics (5F31GM139334-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212353. Licensed CC0.

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