PUBLICATION
The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211
- Authors
- Petersen, S.C., Luo, R., Liebscher, I., Giera, S., Jeong, S.J., Mogha, A., Ghidinelli, M., Feltri, M.L., Schöneberg, T., Piao, X., Monk, K.R.
- ID
- ZDB-PUB-150415-11
- Date
- 2015
- Source
- Neuron 85: 755-69 (Journal)
- Registered Authors
- Mogha, Amit, Monk, Kelly, Petersen, Sarah C.
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Animals, Newborn
- COS Cells
- Cells, Cultured
- Chlorocebus aethiops
- Embryo, Mammalian
- Embryo, Nonmammalian
- Ganglia, Spinal/cytology
- Humans
- In Vitro Techniques
- Laminin/genetics
- Laminin/metabolism*
- Larva
- Mice
- Mice, Inbred C57BL
- Models, Molecular
- Morpholinos/pharmacology
- Myelin Sheath/metabolism*
- Myelin Sheath/ultrastructure
- Neuroglia/metabolism
- Neuroglia/ultrastructure
- Protein Binding/drug effects
- Protein Binding/genetics
- Receptors, G-Protein-Coupled/chemistry
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism*
- Schwann Cells/metabolism*
- Schwann Cells/ultrastructure
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 25695270 Full text @ Neuron
Citation
Petersen, S.C., Luo, R., Liebscher, I., Giera, S., Jeong, S.J., Mogha, A., Ghidinelli, M., Feltri, M.L., Schöneberg, T., Piao, X., Monk, K.R. (2015) The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron. 85:755-69.
Abstract
Myelin ensheathes axons to allow rapid propagation of action potentials and proper nervous system function. In the peripheral nervous system, Schwann cells (SCs) radially sort axons into a 1:1 relationship before wrapping an axonal segment to form myelin. SC myelination requires the adhesion G protein-coupled receptor GPR126, which undergoes autoproteolytic cleavage into an N-terminal fragment (NTF) and a seven-transmembrane-containing C-terminal fragment (CTF). Here we show that GPR126 has domain-specific functions in SC development whereby the NTF is necessary and sufficient for axon sorting, whereas the CTF promotes wrapping through cAMP elevation. These biphasic roles of GPR126 are governed by interactions with Laminin-211, which we define as a novel ligand for GPR126 that modulates receptor signaling via a tethered agonist. Our work suggests a model in which Laminin-211 mediates GPR126-induced cAMP levels to control early and late stages of SC development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping