PUBLICATION
The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 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
-
- Amino Acid Sequence
- Animals
- Axons/metabolism
- Cell Adhesion
- Cell Differentiation
- Cell Proliferation
- Female
- GTP-Binding Protein alpha Subunits, G12-G13/metabolism*
- Gene Expression Regulation, Developmental*
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microscopy, Electron, Transmission
- Molecular Sequence Data
- Monomeric GTP-Binding Proteins/metabolism*
- Mutation
- Myelin Sheath/metabolism
- Neurons/metabolism
- Oligodendroglia/metabolism*
- Receptors, G-Protein-Coupled/metabolism
- Receptors, G-Protein-Coupled/physiology*
- Sequence Homology, Amino Acid
- Zebrafish
- Zebrafish Proteins/metabolism*
- rho GTP-Binding Proteins/metabolism*
- 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 Gα12/13 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