Organ-specific function of adhesion G protein-coupled receptor GPR126 is domain-dependent

Despite their abundance and multiple functions in a variety of organ systems, the function and signaling mechanisms of adhesion G protein-coupled receptors (GPCRs) are poorly understood. Adhesion GPCRs possess large N termini containing various functional domains. In addition, many of them are autop...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-10, Vol.110 (42), p.16898-16903
Main Authors: Patra, Chinmoy, van Amerongen, Machteld J., Ghosha, Subhajit, Ricciardi, Filomena, Sajjad, Amna, Novoyatleva, Tatyana, Mogha, Amit, Monk, Kelly R., Mühlfeld, Christian, Engel, Felix B.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Danio rerio
Developmental biology
Embryos
Endocardium - cytology
Endocardium - embryology
Genotype & phenotype
Heart
HeLa cells
Messenger RNA
Mice
Mice, Knockout
Mitochondria, Heart - genetics
Mitochondria, Heart - metabolism
Models, Biological
Myelination
Myocardium
Organ Specificity - physiology
Phenotypes
Protein Structure, Tertiary
Proteins
Receptors
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Rodents
Schwann cells
Zebrafish
Zebrafish - embryology
Zebrafish - genetics
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary:Despite their abundance and multiple functions in a variety of organ systems, the function and signaling mechanisms of adhesion G protein-coupled receptors (GPCRs) are poorly understood. Adhesion GPCRs possess large N termini containing various functional domains. In addition, many of them are autoproteolytically cleaved at their GPS sites into an N-terminal fragment (NTF) and C-terminal fragment. Here we demonstrate that Gpr126 is expressed in the endocardium during early mouse heart development. Gpr126 knockout in mice and knockdown in zebrafish caused hypotrabeculation and affected mitochondrial function. Ectopic expression of Gpr126-NTF that lacks the GPS motif (NTF ΔᴳᴾS) in zebrafish rescued the trabeculation but not the previously described myelination phenotype in the peripheral nervous system. These data support a model in which the NTF of Gpr126, in contrast to the C-terminal fragment, plays an important role in heart development. Collectively, our analysis provides a unique example of the versatile function and signaling properties of adhesion GPCRs in vertebrates.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1304837110