# Discovering protein networks underlying regulated exocytosis

> **NIH NIH R35** · UNIVERSITY OF COLORADO · 2024 · $161,967

## Abstract

PROJECT SUMMARY
Regulated exocytosis – stimulus-dependent exocytic vesicle fusion – mediates a broad range of fundamental
biological processes including nutrient homeostasis, cell-to-cell signaling, and elimination of transformed or
virally infected cells. Imbalances in these exocytic pathways lead to major forms of human disease. The long-
term goal of this project is to uncover the protein networks governing regulated exocytosis. A major model
pathway we use is insulin-stimulated GLUT4 exocytosis, a physiologically important but poorly characterized
regulated exocytic pathway. We also examine key aspects of other exocytic pathways, aiming to establish
conserved and divergent mechanisms of regulated exocytosis. In our previous research, we carried out CRISPR
genetic screens to systematically dissect insulin-stimulated GLUT4 exocytosis and other exocytic pathways, and
identified a large number of new regulators. In this proposed research, we will carry out in-depth biochemical
and genetic studies to characterize new exocytic regulators isolated in the screens. We will also investigate how
exocytic vesicle fusion is coupled with other cellular processes such as clathrin-mediated endocytosis (CME)
and intracellular signaling to achieve an appropriate exocytic response. In particular, we will examine how AP2
adaptor, a central player in CME, is assembled in the cytosol with the assistance of dedicated assembly
chaperones. Besides these in-depth mechanistic studies, we will continue to identify and validate new regulators
based on candidate genes isolated in our CRISPR screens. The mechanistic studies and CRISPR screens are
fully complementary and will provide a comprehensive understanding of regulated exocytosis that neither
approach alone could generate. Successful completion of this proposed research will fill major gaps in the
knowledge of regulated exocytosis and will serve as a springboard for understanding the molecular basis of
membrane trafficking in general. Ultimately, insights gleaned from this work will facilitate the development of new
therapeutic strategies for diseases caused by dysregulated exocytosis.

## Key facts

- **NIH application ID:** 11097682
- **Project number:** 3R35GM126960-06S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Jingshi Shen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,967
- **Award type:** 3
- **Project period:** 2018-04-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11097682

## Citation

> US National Institutes of Health, RePORTER application 11097682, Discovering protein networks underlying regulated exocytosis (3R35GM126960-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11097682. Licensed CC0.

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