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Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126.
- Source :
-
Science signaling [Sci Signal] 2014 Aug 12; Vol. 7 (338), pp. ra76. Date of Electronic Publication: 2014 Aug 12. - Publication Year :
- 2014
-
Abstract
- GPR126 is an orphan heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) that is essential for the development of diverse organs. We found that type IV collagen, a major constituent of the basement membrane, binds to Gpr126 and activates its signaling function. Type IV collagen stimulated the production of cyclic adenosine monophosphate in rodent Schwann cells, which require Gpr126 activity to differentiate, and in human embryonic kidney (HEK) 293 cells expressing exogenous Gpr126. Type IV collagen specifically bound to the extracellular amino-terminal region of Gpr126 containing the CUB (complement, Uegf, Bmp1) and pentraxin domains. Gpr126 derivatives lacking the entire amino-terminal region were constitutively active, suggesting that this region inhibits signaling and that ligand binding relieves this inhibition to stimulate receptor activity. A new zebrafish mutation that truncates Gpr126 after the CUB and pentraxin domains disrupted development of peripheral nerves and the inner ear. Thus, our findings identify type IV collagen as an activating ligand for GPR126, define its mechanism of activation, and highlight a previously unrecognized signaling function of type IV collagen in basement membranes.<br /> (Copyright © 2014, American Association for the Advancement of Science.)
- Subjects :
- Animals
Biotinylation
Cloning, Molecular
Cyclic AMP metabolism
DNA Primers genetics
Gene Components
Genetic Vectors genetics
HEK293 Cells
Humans
Mutation genetics
Protein Binding
Protein Structure, Tertiary
Rats
Real-Time Polymerase Chain Reaction
Receptors, G-Protein-Coupled genetics
Reverse Transcriptase Polymerase Chain Reaction
Schwann Cells metabolism
Zebrafish
Cell Adhesion physiology
Collagen Type IV metabolism
Ear, Inner embryology
Myelin Sheath metabolism
Receptors, G-Protein-Coupled metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 7
- Issue :
- 338
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 25118328
- Full Text :
- https://doi.org/10.1126/scisignal.2005347