# Using cryo-electron tomography and live-cell fluorescent imaging to study the role of cofilin in regulating neuronal filopodial structure and dynamics

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $397,822

## Abstract

Project Summary/Abstract
How neurons guide their processes to the correct binding partner is a complicated task, but is critical during
development and recovery from injury. It involves the highly coordinated action of many cytoskeletal proteins
and their binding partners within the growth cone at the tips of extending neurites, as they feel their way through
the neuropil. There is a lot known about the signaling pathways that regulate neurite outgrowth and turning, but
the details of how molecular structures come together to achieve growth cone behavior are still unclear. This
project will initially focus on the structure of bundled cofilactin filaments (cofilin-decorated F-actin) in situ, and
how this novel filament structure and fascin cross-linking determine filopodial dynamics. Here we propose that
filopodial behavior is governed partially by the transition from the fascin cross-linked to a cofilin cross-linked
filaments, that makes filopodial bundles more pliable. Experiments are focused around three aims: 1) to study
the high-resolution structure of fascin- and cofilin-linked actin bundles to determine their impact on actin
structure, 2) to determine how changes in fascin and cofilin concentration regulate filopodial dynamics and
structure, and 3) determine how LIMKI and SSH1 form the core of a bidirectional regulatory mechanism for
regulating actin architecture via tuning the phosphorylation state of Ser3 on cofilin.

## Key facts

- **NIH application ID:** 10807055
- **Project number:** 5R01NS126448-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** MATTHEW SWULIUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $397,822
- **Award type:** 5
- **Project period:** 2023-03-15 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807055

## Citation

> US National Institutes of Health, RePORTER application 10807055, Using cryo-electron tomography and live-cell fluorescent imaging to study the role of cofilin in regulating neuronal filopodial structure and dynamics (5R01NS126448-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10807055. Licensed CC0.

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