# Dissecting the mechanistic contributions of Coronin 1B and Coronin 1C to directed cell migration.

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $45,520

## Abstract

Abstract
Effective cell migration is dependent on dynamic remodeling of the actin-cytoskeleton, and plays an essential role in
many physiological events, including tissue morphogenesis, wound healing and inflammatory responses. During these
events, cells are typically directed to migrate towards targets by sensing chemical, physical, mechanical or electrical cues
around them. To facilitate cell migration, actin must undergo rapid cycles of assembly and disassembly in a highly-
coordinated manner. Type I coronins, a conserved class of actin binding proteins, have been shown to regulate the process
of cell migration by modulating the turnover of the branched actin network at the leading edge. Recent work suggests that
the type I coronin, Coronin 1C (Coro1C) mediates the formation of membrane protrusions during cell migration; while the
structurally similar type I coronin Coronin 1B (Coro1B) regulates the disassembly of branched actin networks within
these protrusions. However, despite these results our understanding of the function of Coro1B and Coro1C to actin
dynamics and specifically in directed cell migration remains incomplete. Therefore, the overall objective of this proposal
will be to elucidate the mechanistic contributions of Coro1B and Coro1C in branch stability and de-branching during
directed migration. I hypothesize that Coro1B and Coro1C regulate branched actin dynamics by modulating the functions
of various actin-regulators, including 1) the Arp2/3 complex, 2) cofilin and 3) Rac1 during directed cell migration. To test
this hypothesis, I have established a fibroblast cell line derived from Coro1B knockout (KO), Coro1CFL/FL mice that is
rescued with a flox-able Coro1B-GFP expression construct. Upon Cre-mediated recombination, both exogenous Coro1B-
GFP and endogenous Coro1C are deleted to create a matched-pair null cell line to test the role of coronins in lamellipodial
dynamics and cell motility. In Aim 1, I will utilize the null cells to delineate the mechanistic role of Coro1B and Coro1C
on lamellipodia dynamics using optogenetically controlled Coro1B and Coro1C rescue constructs. In Aim 2, I will utilize
the matched-pair and a microfabrication technique to assess the functional roles of Coro1B and Coro1C in haptotaxis and
chemotaxis, two distinct and clinically relevant forms of directed migration. In all optogenetic and migration experiments
proposed, cellular responses will be measured as changes to cell morphology, cell behavior, and cytoskeletal structure and
organization. These studies will provide fundamental insights into the role of Coro1B and Coro1C in regulating the actin
cytoskeleton during directed cell migration, as well as providing outstanding training opportunities to advance my career
in biomedical science.

## Key facts

- **NIH application ID:** 9995376
- **Project number:** 5F31GM133094-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Zayna T King
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995376

## Citation

> US National Institutes of Health, RePORTER application 9995376, Dissecting the mechanistic contributions of Coronin 1B and Coronin 1C to directed cell migration. (5F31GM133094-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9995376. Licensed CC0.

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