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

Chinmoy Patra, MacHteld J. Van Amerongen, Subhajit Ghosh, Filomena Ricciardi, Amna Sajjad, Tatyana Novoyatleva, Amit Mogha, Kelly R. Monk, Christian Mühlfeld, Felix B. Engel

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55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16898-16903
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number42
DOIs
StatePublished - Oct 15 2013

ASJC Scopus subject areas

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    Patra, C., Van Amerongen, M. J., Ghosh, S., Ricciardi, F., Sajjad, A., Novoyatleva, T., Mogha, A., Monk, K. R., Mühlfeld, C., & Engel, F. B. (2013). Organ-specific function of adhesion G protein-coupled receptor GPR126 is domain-dependent. Proceedings of the National Academy of Sciences of the United States of America, 110(42), 16898-16903. https://doi.org/10.1073/pnas.1304837110