# Mechanism and function of membrane trafficking in dendritic cells

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $236,132

## Abstract

Project summary/abstract
Dendritic cells play an important role in inducing antigen-specific immune responses through the ability to
present antigens to naïve T cells and differentiate them to specific effector cells. This function is profoundly
dependent on proper trafficking of membrane proteins, but the molecular mechanisms that govern the specific
trafficking is not completely understood. Our laboratory is interested in characterizing intracellular trafficking of
membrane proteins playing essential role in dendritic cell function. Our current research is focused on
understanding the mechanism and function of the membrane trafficking mediated by a ubiquitin ligase named
membrane associated RIGN-CH1 (MARCH1). MARCH1 attaches a ubiquitin chain to the cytoplasmic tail of
MHCII and CD86, and this ubiquitination induces endocytosis, lysosomal sorting, and degradation of the
molecules. We have previously found that MARCH1-dependent MHCII ubiquitination is required for dendritic
cell function of selecting regulatory T cells. The mechanisms involved the ubiquitin ligase activity of MARCH1
in maintaining MHCII proteostasis in the plasma membrane of dendritic cells, which was crucial for dendritic
cells to stably engage and activate immature thymocytes for regulatory T cell differentiation. We will investigate
whether this activity also supports dendritic cell function of inducing antigen-specific T cell immunity. In
addition, we will identify new substrates of MARCH1 in dendritic cells and interrogate the molecular
interactions involved in MARCH1’s ubiquitin ligase activity. The information gained from these studies will not
only provide important new insights into the role of MARCH1-dependent membrane trafficking in dendritic cell
function but also improve our understanding on the mechanisms of membrane protein ubiquitination.

## Key facts

- **NIH application ID:** 10105339
- **Project number:** 5R35GM131702-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jeoung-Sook Shin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,132
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105339

## Citation

> US National Institutes of Health, RePORTER application 10105339, Mechanism and function of membrane trafficking in dendritic cells (5R35GM131702-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10105339. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*