PUBLICATION
The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with G?12/13 and RhoA
- Authors
- Ackerman, S.D., Garcia, C., Piao, X., Gutmann, D.H., Monk, K.R.
- ID
- ZDB-PUB-150122-4
- Date
- 2015
- Source
- Nature communications 6: 6122 (Journal)
- Registered Authors
- Monk, Kelly
- Keywords
- Biological sciences, Neuroscience, Developmental biology
- MeSH Terms
-
- Zebrafish Proteins/metabolism*
- Male
- Molecular Sequence Data
- Axons/metabolism
- Animals
- Mice, Inbred C57BL
- Sequence Homology, Amino Acid
- Cell Differentiation
- Gene Expression Regulation, Developmental*
- GTP-Binding Protein alpha Subunits, G12-G13/metabolism*
- Cell Proliferation
- Zebrafish
- Cell Adhesion
- Oligodendroglia/metabolism*
- Myelin Sheath/metabolism
- Neurons/metabolism
- Mice, Knockout
- Female
- Mutation
- rho GTP-Binding Proteins/metabolism*
- Monomeric GTP-Binding Proteins/metabolism*
- Mice
- Receptors, G-Protein-Coupled/metabolism
- Receptors, G-Protein-Coupled/physiology*
- Microscopy, Electron, Transmission
- Amino Acid Sequence
- PubMed
- 25607772 Full text @ Nat. Commun.
Citation
Ackerman, S.D., Garcia, C., Piao, X., Gutmann, D.H., Monk, K.R. (2015) The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with G?12/13 and RhoA. Nature communications. 6:6122.
Abstract
In the vertebrate central nervous system, myelinating oligodendrocytes are postmitotic and derive from proliferative oligodendrocyte precursor cells (OPCs). The molecular mechanisms that govern oligodendrocyte development are incompletely understood, but recent studies implicate the adhesion class of G protein-coupled receptors (aGPCRs) as important regulators of myelination. Here, we use zebrafish and mouse models to dissect the function of the aGPCR Gpr56 in oligodendrocyte development. We show that gpr56 is expressed during early stages of oligodendrocyte development. In addition, we observe a significant reduction of mature oligodendrocyte number and myelinated axons in gpr56 zebrafish mutants. This reduction results from decreased OPC proliferation, rather than increased cell death or altered neural precursor differentiation potential. Finally, we show that these functions are mediated by Gα12/13 proteins and Rho activation. Together, our data establish Gpr56 as a regulator of oligodendrocyte development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping