# Role of Membrane Trafficking in Epithelial Homeostasis

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $17,686

## Abstract

Epithelial cells play critical roles in many organs and are responsible for elemental processes such as nutrient
uptake and waste product secretion. To fulfill these functions, they polarize their plasma membrane into apical
and basolateral domains. To maintain tissue homeostasis, epithelial cells must continuously sort newly
synthesized and internalized surface receptors to the correct target domain. And after tissue damage, epithelial
cells must correctly migrate into the wound and re-colonize the wound area. Loss of polarity is associated with
numerous diseases including metastatic cancer, polycystic kidney disease, and Crohn’s disease. How epithelial
cell polarity is regulated is thus an important cell biological question with profound implications for human health.
Our work identified the epithelial cell-specific clathrin adaptor complex AP-1B as crucial for polarized recycling
of cargos to the basolateral domain. Cargos that depend on AP-1B for basolateral localization include important
signaling receptors such as epidermal growth hormone receptor whose missorting to the apical domain has been
implicated in cancer and polycystic kidney disease, and toll-like receptor 3 whose missorting results in chronic
inflammation. A major unresolved question in the field is how AP-1B uniquely functions in epithelial cells, and
why its close cousin AP-1A mostly fails to substitute. Our previous work suggested that AP-1B changes the
organization of recycling endosomes (REs) to accommodate AP-1B’s function in basolateral sorting. Only AP-
1B but not AP-1A localizes in REs where it triggers the formation of a lipid domain enriched in PI(3,4,5)P3, and
facilitates the recruitment of accessory factors including a vesicle-tethering complex (the exocyst) and a lipid
kinase (PIPKIg-90). We recently showed that AP-1B expression reduced the speed of collective cell migration
after monolayer wounding, a novel function independent of basolateral sorting. We will test the central hypothesis
that AP-1B plays dual roles in establishment and maintenance of epithelial monolayers by 1) directing cargos to
the basolateral membrane by generating a sorting platform in REs at steady-state and 2) during cell migration
by modulating the availability of focal adhesion molecules at the plasma membrane. We will test this hypothesis
in our proposed experiments by using state-of-the-art imaging techniques including live TIRF microscopy in
combination with photoactivation and unbiased screens including BioID and mass spectrometry to complement
innovative cell biological and biochemistry approaches to: 1. Determine how AP-1B generates a basolateral
sorting platform, and 2. Determine how AP-1B controls cell migration. Our studies will define new mechanisms
governing the organization of polarized epithelial cells at steady-state and during cell migration.

## Key facts

- **NIH application ID:** 10796580
- **Project number:** 3R01GM141233-02S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** HEIKE FOLSCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $17,686
- **Award type:** 3
- **Project period:** 2022-01-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796580

## Citation

> US National Institutes of Health, RePORTER application 10796580, Role of Membrane Trafficking in Epithelial Homeostasis (3R01GM141233-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10796580. Licensed CC0.

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