# Endosomes as a multifunctional hub to control GPCR function

> **NIH NIH R35** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $384,997

## Abstract

Project Summary/Abstract
GPCRs are the largest family of membrane bound signaling molecules and, collectively, the target of many
drugs currently used in the clinic. Classically, GPCRs were thought to be active at the cell surface and inactive
while undergoing molecular sorting and trafficking events within the cell. Recent work has overturned this
model. GPCRs are not quiescent inside of cells. Instead, it is now known that GPCRs can activate G protein
signaling from many intracellular compartments including the endosome, and this intracellular signaling
changes drug response. While efforts are already underway to harness endosomal GPCR signaling as a drug
target, much is unknown about GPCR sorting at endosomes and how these trafficking processes control
endosomal GPCR signaling. The goal of this proposal is to address the knowledge gap surrounding GPCR
sorting at endosomes, and to determine how these pathways control endosomal signaling. In Project 1 we test
the hypothesis that endosomal sorting functions as a kinetic timer to control GPCR signaling at endosomes.
We examine a prototypical GPCR, the beta 2 adrenergic receptor, and the use a combination of genetic
engineering and proteomics to determine how sorting controls endosomal signaling. In Project 2 we focus on
two different GPCRs which signal at endosomes but lack any of the consensus endosomal sorting motifs. We
use a combination of chemical biology, genomics, and proteomics to identify the proteins and pathways which
mediate endosomal sorting of these receptors. Our studies seek to reveal fundamental lessons about
conserved cell biological pathways while driving forward a new area for future GPCR drug development.

## Key facts

- **NIH application ID:** 10201677
- **Project number:** 5R35GM137835-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Braden Lobingier
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,997
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201677

## Citation

> US National Institutes of Health, RePORTER application 10201677, Endosomes as a multifunctional hub to control GPCR function (5R35GM137835-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201677. Licensed CC0.

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