title: The multiple signaling modalities of adhesion G protein-coupled receptor GPR126 in development.
abstract: The G protein-coupled receptor (GPCR) superfamily is the largest known receptor family in the human genome. Although the family of adhesion GPCRs comprises the second largest sub-family, their function is poorly understood. Here, we review the current knowledge about the adhesion GPCR family member GPR126. GPR126 possesses a signal peptide, a 7TM domain homologous to secretin-like GPCRs, a GPS motif and an extended N-terminus containing a CUB (Complement, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a hormone binding domain and 27 putative N-glycosylation sites. Knockdown and knockout experiments in zebrafish and mice have demonstrated that Gpr126 plays an essential role in neural, cardiac and ear development. In addition, genome-wide association studies have implicated variations at theGPR126locus in obstructive pulmonary dysfunction, in scoliosis and as a determinant of trunk length and body height. Gpr126 appears to exert its function depending on the organ system via G protein- and/or N-terminus-dependent signaling. Here, we review the current knowledge about Gpr126, which, due to the variety of its functions and its multiple signaling modalities, provides a model adhesion GPCR to understand general functional concepts utilized by adhesion GPCRs.
authors.affiliation: Department of Developmental Genetics, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: Chinmoy
authors.initials: C
authors.lastname: Patra
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Monk
authors.affiliation: Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, University of Erlangen-Nürnberg, Universitätsstraße 22, 91054 Erlangen, Germany.
authors.forename: Felix B
authors.initials: FB
authors.lastname: Engel
keywords: CTF; GAIN; GPR126; GPS; NTF; adhesion GPCR; ear; heart; myelination