# Compartmentalized signaling and crosstalk in airway myocytes

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2024 · $543,494

## Abstract

PROJECT SUMMARY/ABSTRACT
 This basic science grant seeks to determine fundamental mechanisms as to how a physiologically relevant
cell controls the subcellular location of a signal to optimize the effect of that signal on cell function. We propose
to build on recent findings by our diverse investigative team to delineate how 3 different Gs-coupled receptors in
airway smooth muscle (ASM) cells - the 2AR, EP2, and EP4 receptors- have their signals compartmentalized
within the cell to regulate important ASM cell functions. Aim 1 will employ novel imaging approaches to delineate
spatiotemporal features of cAMP/PKA signaling by each receptor and demonstrate how this compartmentalized
signaling is shaped by receptor-specific complements of AKAP and PDE isoforms, and by the competing co-
activated Gq-coupled receptor. Aim 1 will also employ multiple subcellular-targeted biosensors to characterize
the capacity of each receptor to signal from intracellular membrane compartments. Aim 2 will assess how these
different receptors generate unique phosphoproteome signatures, and how manipulating the mechanisms
shaping localized cAMP/PKA signaling regulates these signatures. Aim 3 will establish how the mechanisms
dictating spatiotemporal features of ASM cAMP and the ASM proteome affect Gs-coupled GPCR regulation of
ASM contraction, migration, and synthetic functions. The proposed studies will provide a foundation for
understanding compartmentalized signaling in the form of both methodological advances and the knowledge
gained in how Gs-coupled receptors employ distinct signaling mechanisms to render efficient and specific
functional effects. From a translational perspective, our findings will constitute a critical basic science foundation
for developing new drugs that target mechanisms of signaling compartments, most readily applied to better
control asthma features such as airway hyperresponsiveness, airway remodeling, and possibly airway
inflammation.

## Key facts

- **NIH application ID:** 10857217
- **Project number:** 5R01HL169522-02
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** RENNOLDS S OSTROM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $543,494
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857217

## Citation

> US National Institutes of Health, RePORTER application 10857217, Compartmentalized signaling and crosstalk in airway myocytes (5R01HL169522-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10857217. Licensed CC0.

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