# Investigating the role of EPS8 in microvillar growth

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $30,736

## Abstract

PROJECT SUMMARY/ABSTRACT
Microvilli are actin-based protrusions located at the apical surface of transporting epithelial cells. In the context
of the mammalian intestine, microvilli collectively comprise the intestinal brush border, which acts as a first line
of defense against pathogens and increases the surface are for nutrient absorption. Despite the importance of
microvilli for intestinal health and human viability, little is known about the molecular events that underlie
microvillar assembly. Early ultrastructural analysis by transmission electron microscopy revealed that the distal
tips of microvilli are occupied by an electron dense plaque known as the “distal tip complex”, which embeds the
barbed ends of actin filaments. As the barbed ends of actin filaments are the preferred site of actin monomer
addition, proteins that regulate actin filament length typically target to these ends. One candidate distal tip
complex protein is epidermal growth factor receptor pathway substrate 8 (EPS8). Intestinal tissue staining of
EPS8 revealed striking distal tip localization along the length of the intestinal crypt-villus. Additionally, the domain
architecture of EPS8 lends the potential to bind plasma membrane, actin, and other signaling factors, features
that position it as an attractive candidate for orchestrating microvillar assembly. Moreover, studies have shown
that loss of EPS8 in both cell culture and mouse knockout models results in shortened microvilli. Despite these
findings, how EPS8 promotes microvillar growth remains unknown. Thus, this proposal seeks to define the
mechanism by which EPS8 promotes microvillar growth using live cell, super resolution, and transmission
electron microscopy in combination with molecular biology techniques. Moreover, as EPS8 is remarkably specific
to the distal tips of microvilli, this specificity can be harnessed to define other distal tip complex proteins with a
biotin proximity labeling approach. By creating a chimeric fusion with the biotin ligase BioID2 (EPS8-BioID2),
proteins residing in the distal tip complex can be biotinylated, isolated, and identified by mass spectrometry. As
such, revealing the identity of distal tip complex proteins would provide insight into the general mechanism of
microvillar growth, a process essential for normal brush border physiology. Thus, understanding mechanisms
underlying microvillar growth can provide insight into diseases where microvillar morphology is compromised,
such as microvillus inclusion disease, celiac disease, and Chron’s disease.

## Key facts

- **NIH application ID:** 10164775
- **Project number:** 5F31DK122692-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Isabella M Gaeta
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,736
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164775

## Citation

> US National Institutes of Health, RePORTER application 10164775, Investigating the role of EPS8 in microvillar growth (5F31DK122692-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10164775. Licensed CC0.

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