# Dynamic Regulation of the Actin Filament Barbed End

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $300,138

## Abstract

Project Summary
Actin is a key protein for normal cell function, and the ability to control the polymerization of
actin filaments is essential in the cell. Actin assembles into filaments with two distinct ends, and
most of this control happens at what is termed the plus or barbed end of the filament. Two key
proteins function at the barbed end: capping protein and formins. As suggested by its name,
capping protein “caps” the barbed end and prevents further polymerization, but the activity of
capping protein is also regulated by the action of proteins such as myotrophin/V-1, CARMIL and
twinfilin. Formins have the opposite effect of capping protein and enhance polymerization at the
barbed end. However, just as capping protein is regulated, the function of the formin INF2 is
modulated by cyclase-associated protein (CAP) as well as post-translational modifications to
actin.
The focus of this proposal is to understand the structural, dynamical and functional mechanisms
that regulate the barbed end of the filament. Through a combination of computational, in vitro
and in vivo studies we will: (a) gain new understanding of what defines the barbed end and how
it is affected by the nucleotide state of actin; (b) learn how capping protein interacts with the
barbed end and how this interaction is affected by the steric and allosteric effects of V-1,
CARMIL and twinfilin; and (c) determine how INF2 interacts with the barbed and how both CAP
and lysine methylation of actin alter this interaction.

## Key facts

- **NIH application ID:** 10127677
- **Project number:** 5R01GM136822-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** David Sept
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,138
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127677

## Citation

> US National Institutes of Health, RePORTER application 10127677, Dynamic Regulation of the Actin Filament Barbed End (5R01GM136822-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10127677. Licensed CC0.

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