# Mechanisms and function of spatially encoded GPCR signaling

> **NIH NIH R35** · DUKE UNIVERSITY · 2021 · $402,500

## Abstract

Mechanisms and function of spatially encoded GPCR signaling
PROJECT SUMMARY: G protein-coupled receptors (GPCRs), a critical class of signal transducers, are
ubiquitously expressed in the human body and can detect virtually all types of stimuli. As such, these
transmembrane receptors control all essential human physiology, and account for almost half of current
therapeutic targets. All of the known drugs acting on GPCRs were developed on the assumption that
signals initiated at the cell surface were the primary process that needed to be regulated. However,
recent work by us and others has upended this `classical' model of GPCR signal transduction by
demonstrating that receptors can be active inside the cell. Furthermore, we have established that
localization of the active GPCR can specify functionally distinct cellular responses and could shape how
cells interpret different drugs acting through the same receptor. Leveraging the insights from these
findings, we aim to provide a comprehensive dissection of the cellular functions and molecular
underpinnings of compartmentalized GPCR signaling. Specifically, in this proposal we will dissect how
spatially encoded responses are established across multiple levels, from molecular determinants within
the GPCR itself, to downstream effectors, and cell-type specific mechanisms. Further, we will carry out
comprehensive analysis of the downstream responses triggered by known compartments of receptor
activity to determine the consequences of localized signaling. This proposal is anchored in our
strengths in high-throughput quantitative methods, imaging, pharmacology, and cell biology. These
studies will elucidate fundamental principles governing cellular signal transduction, and allow us to re-
explore the molecular determinants of GPCR pharmacology in order to effectively target these
pathways in disease.

## Key facts

- **NIH application ID:** 10274383
- **Project number:** 1R35GM142640-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Nikoleta Georgieva Tsvetanova
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $402,500
- **Award type:** 1
- **Project period:** 2021-08-01 → 2022-06-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274383

## Citation

> US National Institutes of Health, RePORTER application 10274383, Mechanisms and function of spatially encoded GPCR signaling (1R35GM142640-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10274383. Licensed CC0.

---

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