# Autophagy and LC3-associated phagocytosis in intestinal epithelial cells

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2023 · $450,877

## Abstract

Abstract
The intestinal epithelium is vital to maintain the barrier between the body and the outside world, and membrane
trafficking is essential for both the development and maintenance of this barrier. Abnormal membrane
trafficking can result compromised barrier leading to intestinal disease, including inflammatory bowel disease.
Autophagy is a specialized membrane trafficking process that allows cells to respond to changes in
metabolism. In addition, autophagy is important for maintenance of the epithelial barrier and the innate immune
response, mediating the isolation and degradation of intracellular pathogens. Furthermore, LC3-associated
phagocytosis (LAP) is important for uptake and degradation of pathogens, and dysfunction of this pathway is
associated with hyperinflammation. Importantly, variants of proteins in the autophagic and LAP pathways have
been linked to increased susceptibility to Inflammatory Bowel Disease (IBD), and particularly Crohn’s disease,
although the molecular mechanisms that underlie this connection remain incompletely understood. MAMDC4 is
an integral membrane protein that localizes to endosomes of the intestinal epithelium. Deletion of MAMDC4
compromises intestinal enterocyte morphology, and RNAseq studies have indicated that MAMDC4 is down-
regulated in IBD. In previous work, we found that MAMDC4 interacts with the small GTPase Rab14. In
professional phagocytes, Rab14 is recruited to phagosomes and prevents phagosome-lysosome fusion but its
role in the intestinal epithelium is unknown. In our preliminary data, we show that Rab 14 is present on
autophagosomes and both Rab14 and MAMDC4 are present on membranes containing invading bacteria.
Furthermore, deletion of MAMDC4 results in accumulation of autophagy and lysosomal markers on tubular
membranes. These results suggest that MAMDC4 and Rab14 act in a molecular network to maintain mucosal
immunity through control of autophagy or LAP. In this proposal we will use intestinal epithelial cells in culture,
organoid culture, and patient-derived organoids to define the role of autophagy and/or LAP in intestinal
homeostasis.

## Key facts

- **NIH application ID:** 10671568
- **Project number:** 5R01DK132074-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jean M Wilson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $450,877
- **Award type:** 5
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10671568

## Citation

> US National Institutes of Health, RePORTER application 10671568, Autophagy and LC3-associated phagocytosis in intestinal epithelial cells (5R01DK132074-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10671568. Licensed CC0.

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