# The role of GPR56 in platelet function

> **NIH NIH F32** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $68,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Adhesion G protein-coupled receptors (aGPCRs) are the second largest subset of the GPCR superfamily,
comprising of 33 members that can be subdivided into nine subfamilies. Majority of the receptors in this subset
have varying length of the N-termini with a GPCR-autoproteolysis-inducing (GAIN) domain that mediates self-
cleavage into two cleaved receptor protomers, the N-terminal fragment (NTF) and the cytoplasmic C-terminal
fragment (CTF), that remain noncovalently associate with each other on the plasma membrane. Previously, we
had identified that urea-dissociation of the NTF unveils a cryptic N-terminal stalk, encompassing the tethered
peptide agonist region, that acts on the seven transmembrane (7TM) to activate G protein signaling. Although
the biochemical dissociation of the NTF of aGPCR, provided invaluable insight into a tethered-peptide-agonist
mechanism, the physiological mechanism that supports this remains unknown. We postulate that a shear-force
induced mechanism would dissociate the NTF to reveal the tethered-peptide agonist to activate aGPCR. We
have identified platelets that endogenously express aGPCR, GPR56, which is known to interact with collagen,
to be an ideal model to investigate our proposed shear-force induced mechanism of NTF removal from GPR56.
This model will also facilitate in further elucidating the role of GPR56 in platelet function, especially in hemostasis
and thrombosis. In addition to the in vitro shear-force dissociation approaches, ex vivo and in vivo mouse models
of hemostasis and thrombosis will be employed to aid in understanding and validating the underlying mechanism
of GPR56 mode of activation. Importantly this project underlies the utility of a tethered-peptide-agonist
mechanism as a tool to study aGPCR activation and identify novel receptors on an endogenous cell system.
Understanding the mechanism of aGPCR, such as GPR56, activation in platelets may lead to new therapeutic
drug design to treat aberrant platelet-related disorders, bleeding and thrombotic-complications.

## Key facts

- **NIH application ID:** 10300401
- **Project number:** 7F32HL149280-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jennifer Yeung
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,000
- **Award type:** 7
- **Project period:** 2019-07-31 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300401

## Citation

> US National Institutes of Health, RePORTER application 10300401, The role of GPR56 in platelet function (7F32HL149280-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10300401. Licensed CC0.

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