# Adhesion G Protein-Coupled Receptors in CNS Development and Regeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $579,977

## Abstract

Myelin is the multilamellar membrane generated by glial cells that insulates, nourishes and protects axons
in the vertebrate nervous system. In the central nervous system (CNS), oligodendrocytes (OLs) form the
myelin sheath. OL follow an orderly and distinct developmental pattern with stage-specific functions. OL
precursor cell (OPC) proliferate. Pre-myelinating OL (pmOL) mediate initial axon ensheathment and
myelinating OL (mOL) carry out iterative axon wraps. Our published work demonstrates that G protein-coupled receptor (GPCR) GPR56 regulates OPC proliferation by mediating a tripartite signaling between
OPC GPR56, microglia-derived tissue transglutaminase, and matrix protein laminin-111. Intriguingly, single
cell RNAseq data reveals that, within the OL lineage, GPR56 is expressed highest at the pmOL stage. Our
unpublished data provide tantalizing evidence that (1) pmOL GPR56 is required for F-actin formation;
(2) deleting Gpr56specifically in pmOLs results in reduced myelination of the corpus callosum (CC); and (3)
pmOLs lacking Gpr56 were unable to form myelin in co-cultured Shiverer cerebellar slices. Taking these
data all together, we hypothesize that GPR56 functions in pmOLs to regulate actin organization of the pre-myelinating OL process. This proposal is designed to test this hypothesis, thus establishing novel GPCR
signaling pathway in pmOL F-actin polymerization and axon ensheathment. Our data will enhance the
understanding of the basic biology of myelination and will potentially reveal a new target for therapeutics to
promote repair in the wide spectrum of neurological diseases that implicate myelin damage.

## Key facts

- **NIH application ID:** 10417182
- **Project number:** 5R01NS094164-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Xianhua Piao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $579,977
- **Award type:** 5
- **Project period:** 2015-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417182

## Citation

> US National Institutes of Health, RePORTER application 10417182, Adhesion G Protein-Coupled Receptors in CNS Development and Regeneration (5R01NS094164-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10417182. Licensed CC0.

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