TY - JOUR
T1 - Organ-specific function of adhesion G protein-coupled receptor GPR126 is domain-dependent
AU - Patra, Chinmoy
AU - Van Amerongen, MacHteld J.
AU - Ghosh, Subhajit
AU - Ricciardi, Filomena
AU - Sajjad, Amna
AU - Novoyatleva, Tatyana
AU - Mogha, Amit
AU - Monk, Kelly R.
AU - Mühlfeld, Christian
AU - Engel, Felix B.
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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 Cterminal 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.
AB - 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 Cterminal 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.
UR - http://www.scopus.com/inward/record.url?scp=84885639028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885639028&partnerID=8YFLogxK
U2 - 10.1073/pnas.1304837110
DO - 10.1073/pnas.1304837110
M3 - Article
C2 - 24082093
AN - SCOPUS:84885639028
SN - 0027-8424
VL - 110
SP - 16898
EP - 16903
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 42
ER -