# Molecular mechanisms of bundled actin structure assembly by formins

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $286,465

## Abstract

PROJECT SUMMARY
Cells dynamically assemble a diverse set of actin-based structures to perform essential processes including
motility, division and signaling. One class of actin structures consists of networks of actin filaments that are
bundled together into parallel or anti-parallel architectures. These bundled actin structures include contractile
rings, actin cables, filopodia, and the stress fibers that promote focal adhesion maturation and nuclear
positioning. The actin filaments that comprise these structures are primarily polymerized by formins, a family of
proteins that nucleate and direct the elongation of unbranched actin filaments. Mammals express 15 formin
isoforms, each of which possesses unique actin assembly properties and plays a specific role in cells.
Although mutations in formin genes are associated with a number of human diseases including preleukemic
disorders and cancer, it remains unknown how the polymerization activity of each formin isoform is tuned for
the assembly of a specific bundled actin structure and participation in a specific cellular process. To bridge this
gap in understanding, we must establish how formins function in the context of the bundled actin structures
that exist in cells. We will address this question by characterizing the mechanism of formin-mediated assembly
of bundled actin structures. Our central hypothesis is that incorporation of formin-bound actin filaments into
bundled structures modulates polymerization by exposing formins to force, filament bundling and filament
severing. We will use a combination of biophysical and cell biological approaches to test this hypothesis by
pursuing three specific aims: (1) To elucidate the effects of force on the mechanism of formin-mediated
filament elongation, (2) to investigate the relationship between filament bundling and formin polymerization
activity, and (3) to evaluate the contribution of filament turnover to bundled actin structure assembly. By
establishing the mechanism of formin-directed bundled actin assembly, we will gain fundamental insights into
the large number of cellular processes regulated by formins. This work will also provide a molecular basis for
understanding how formins contribute to healthy cellular proliferation and normal development.

## Key facts

- **NIH application ID:** 10216284
- **Project number:** 5R01GM122787-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Naomi Courtemanche
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $286,465
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216284

## Citation

> US National Institutes of Health, RePORTER application 10216284, Molecular mechanisms of bundled actin structure assembly by formins (5R01GM122787-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10216284. Licensed CC0.

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