# GPCR anterograde trafficking

> **NIH NIH R35** · AUGUSTA UNIVERSITY · 2021 · $230,000

## Abstract

Summary
 G protein-coupled receptors (GOCRs) regulate a variety of cell functions and are important targets of
therapeutics. A fundamental but poorly understood question in studying GPCRs is how targeted GPCR
trafficking is achieved. The overall goal of our research program is to elucidate the molecular mechanisms
of nascent GPCR targeting to their functional destinations and to understand the role of targeting in
modulating cellular responses to hormones and drugs. Under this broad objective, this proposal will use α2-
adrenergic receptors (α2-ARs) as models to address the following two questions which are central to
understanding GPCR anterograde trafficking: 1) how newly synthesized GPCRs export from the
endoplasmic reticulum (ER) and then transport en route from the ER through the Golgi to the cell surface;
and 2) how GPCRs are sorted from one another and from non-GPCR plasma membrane proteins during
their traffic along the biosynthetic pathway. The premise of this project is our recent findings that the ER-
Golgi-cell surface transport and sorting of α2A-AR and α2B-AR, two closely related, prototypic GPCRs, are
coordinated by ufmylation, an ubiquitination-like post-translational modification, and three interacting
proteins, C1orf27 (an ER membrane protein), coiled-coil α-helical rod protein 1 (HCR1) and Golgi-localized γ
ear-containing ARF-binding protein 3 (GGA3). We will define the novel functions of protein ufmylation and
C1orf27 in the ER-Golgi transport and sorting, as well as HCR1 and GGA3 in the post-Golgi traffic and
sorting of α2A-AR and α2B-AR, and elucidate the underlying mechanisms. The proposed research is a
continuation of our long-standing efforts to study the anterograde trafficking of GPCRs, which have led to
the discovery of a number of structural determinants and regulatory proteins essential for GPCR export and
sorting. As in the past, we will employ state-of-the-art biochemical, immunochemical and live cell imaging
techniques to dissect the mechanistic aspects of GPCR trafficking along the biosynthetic pathway, including
maturation, sorting and targeting. These studies will provide important insights into regulation of GPCR
export trafficking which is a poorly explored area in the study of the GPCR superfamily.

## Key facts

- **NIH application ID:** 10388443
- **Project number:** 3R35GM136397-02S1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** GUANGYU WU
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $230,000
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388443

## Citation

> US National Institutes of Health, RePORTER application 10388443, GPCR anterograde trafficking (3R35GM136397-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10388443. Licensed CC0.

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