# Prostaglandins and actin remodeling

> **NIH NIH R35** · UNIVERSITY OF IOWA · 2022 · $550,634

## Abstract

All eukaryotic cells produce and respond to prostaglandin (PG) signaling. PGs are lipid signaling molecules that
have a wide range of functions from inflammation to fertility to wound healing. Imbalances in PG signaling underly
many diseases, such as birth defects, cardiovascular disease, and cancer. PGs have such wide effects because
there are 5 types of PGs, and each activates multiple signaling cascades. All PGs are produced by a multistep
process that requires cyclooxygenase (COX) enzymes. COX enzymes are the targets of the commonly used
non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. Thus, NSAIDs block all PG
synthesis and signaling. To develop more specific therapies and to better understand the functions of PGs, it is
essential to uncover the cellular roles of PG signaling. One understudied cellular function of PGs is to regulate
actin remodeling to promote collective cell migration. While over 50,000 studies have uncovered critical
regulators of cell migration, less than 60 studies have focused on the roles of PGs in this process. Thus, how
PGs regulate actin remodeling and migration remains elusive. The roles of individual PG signaling pathways,
and whether they act in the migratory cells or their substrate to coordinate cell migration are poorly understood.
Further, the specific actin regulators that are the downstream effectors of PG signaling, and how they are
modulated, are largely unknown. To overcome these knowledge gaps, we take advantage of the robust system
of Drosophila and the in vivo, collective migration of the border cells during oogenesis. In the last five years, we
found that PG synthesis in the border cells promotes on-time migration, whereas PG synthesis in the substrate
controls border cell cluster cohesion. We identified that one downstream target of PGs in both the border cells
and their substrate is Fascin. In addition to bundling actin, we found Fascin regulates the transmission of force
to the nucleus by promoting the activity of the Linker of the Nucleoskeleton and Cytoskeleton (LINC) Complex,
and the transmission of force between cells by inhibiting myosin. Using genetic, cellular, biochemical, and
biophysical approaches, the proposed studies are expected to build a new paradigm for how PG signaling, and
its effects on Fascin, coordinate the behaviors of migrating cells and their cellular substrates to promote collective
cell migration. We propose to address: 1) Which PG signaling cascades act in the migratory cells versus their
substrate to regulate collective cell migration? 2) How does PG signaling regulate Fascin? 3) What is the role of
PG signaling in LINC Complex-mediated mechanotransduction during migration? 4) How does PG signaling
control the balance of forces between the migratory cells and their substrate during collective cell migration?
Through this work, we expect to fundamentally advance our mechanistic understanding of how multiple PG
signaling pathways and Fascin me...

## Key facts

- **NIH application ID:** 10328668
- **Project number:** 1R35GM144057-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Tina L Tootle
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $550,634
- **Award type:** 1
- **Project period:** 2022-03-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328668

## Citation

> US National Institutes of Health, RePORTER application 10328668, Prostaglandins and actin remodeling (1R35GM144057-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328668. Licensed CC0.

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