# Investigation of a Newly Discovered Organelle-Based Signaling Paradigm

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $411,681

## Abstract

Project summary/Abstract
My research program investigates cellular architecture as a key factor in signal transduction. A
long-held tenet of molecular pharmacology is that receptors at the cell surface are the sole site of
action of external, plasma membrane impermeable ligands such as peptide/protein-derived
hormones and biogenic amines. Therefore, understanding of the immediate consequences of
signaling has largely been confined to events that happen proximal to the plasma membrane.
The work from my lab suggests that these are narrow views of how signaling receptors function.
By developing novel tools to visualize signaling in intact cells and focusing on a class of G protein
coupled receptors (GPCRs), we have shown that 1) receptor activation and subsequent G protein-
mediated signaling occurs not only at the plasma membrane but also at previously unappreciated
subcellular compartments such as the endosomes and the Golgi membranes, 2) signaling from
these internal compartments constitutes a critical aspect of cellular responses to external cues,
3) transport mechanisms allow membrane impermeable ligands to access compartments within
the cell, 4) efficacies of certain clinically used drugs may be driven from their serendipitous
capacity to cross the plasma membrane and act on internal receptor pools, and that 5) receptor
activation at each subcellular membrane compartment recruits a unique set of effectors/proteins
via distinct lipid environment at each location. Subcellular, compartmentalized signaling by
GPCRs is a new and largely unappreciated facet of cellular signaling with major implications for
physiology and pathophysiology. My goal is to investigate spatially distinct subcellular
compartments as signaling hubs. We will decipher the factors that initiate signaling at each
signaling hub and determine how each compartment achieves specialized molecular and cellular
outcomes, and how this knowledge can provide a framework for developing therapeutics that
selectively act on compartment specific aspects of signaling.

## Key facts

- **NIH application ID:** 10842110
- **Project number:** 2R35GM133521-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Roshanak Irannejad
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,681
- **Award type:** 2
- **Project period:** 2019-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842110

## Citation

> US National Institutes of Health, RePORTER application 10842110, Investigation of a Newly Discovered Organelle-Based Signaling Paradigm (2R35GM133521-06). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10842110. Licensed CC0.

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