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The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211.
- Source :
-
Neuron [Neuron] 2015 Feb 18; Vol. 85 (4), pp. 755-69. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- 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
Larva
Mice
Mice, Inbred C57BL
Models, Molecular
Morpholinos pharmacology
Myelin Sheath ultrastructure
Neuroglia metabolism
Neuroglia ultrastructure
Protein Binding drug effects
Protein Binding genetics
Receptors, G-Protein-Coupled chemistry
Receptors, G-Protein-Coupled genetics
Schwann Cells ultrastructure
Zebrafish
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Laminin metabolism
Myelin Sheath metabolism
Receptors, G-Protein-Coupled metabolism
Schwann Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 85
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 25695270
- Full Text :
- https://doi.org/10.1016/j.neuron.2014.12.057