LGR7‐Truncate Is a Splice Variant of the Relaxin Receptor LGR7 and Is a Relaxin Antagonist in Vitro

Abstract

The relaxin receptor (LGR7) and the insulin-like peptide 3 (INSL3) receptor (LGR8) are unique LGR family members in possessing a single, functionally important amino terminal LDL-A module.1 Mouse and rat cDNA was screened for LGR7 and LGR7 splice variant expression. A uterus-specific exon 4 deleted variant was identified and named LGR7-Truncate. Deletion of exon 4 results in a premature stop codon and a transcript that putatively encodes a secreted protein containing LGR7's LDL-A module. Expression of LGR7-Truncate with LGR7 in HEK-293T cells resulted in decreased relaxin-induced signaling of LGR7. LGR7-Truncate is potentially an endogenous regulator of LGR7 signaling.

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

“…More recent studies used a panel of GPCR-relevant signaling reporter genes to demonstrate that the RXFP1 receptor lacking the LDLa module does not signal through any pathway tested . Importantly, a soluble recombinant form of the RXFP1 LDLa module acts as an RXFP1 antagonist when introduced into cells expressing RXFP1 (Scott et al, 2005c. These data suggest that the LDLa module may act as an RXFP1 tethered ligand and its actions can be blocked by the addition of recombinant LDLa.…”

International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

“…LDLa is the unique N-terminal region found in type C-glycoprotein receptors; the RXFP1-truncate is a naturally occurring splice variant of the receptor that includes the LDLa region and acts as a functional antagonist at the RXFP1 receptor (Scott et al, 2005c a Genes for rat and mouse relaxin are named RLN1 in the databases but are the rodent equivalents of RLN2 in the human. b INSL5 is a pseudogene in the rat (Liu et al, 2005).…”

“…An aspartic acid residue (RXFP1-D637; RXFP2-D647), which when mutated to a tyrosine results in constituitive cAMP activity for both receptors, is marked (F) . 20 isoforms of the receptors can be generated (Muda et al, 2005;Scott et al, 2005c). An exon 4-deleted RXFP1 splice variant has been discovered in mouse, rat, and pig (Scott et al, 2005c).…”

“…20 isoforms of the receptors can be generated (Muda et al, 2005;Scott et al, 2005c). An exon 4-deleted RXFP1 splice variant has been discovered in mouse, rat, and pig (Scott et al, 2005c). Removal of exon 4 causes a frameshift, resulting in a premature stop codon and production of a truncated protein (RXFP1-truncate) that encodes primarily the LDLa module without the LRRs or transmembrane region.…”

Characterization of Novel Splice Variants of LGR7 and LGR8 Reveals That Receptor Signaling Is Mediated by Their Unique Low Density Lipoprotein Class A Modules

“…We have * This work was supported in part by an Australian National Health and Med-previously reported the identification of an LGR7 splice variant in rodents that is missing exon 4 and named LGR7-truncate (33). LGR7-truncate is expressed in the reproductive tract of late stage pregnant mice and rats (33), and an expressed sequence tag clone (BF191498) from a pooled library of male and female pig reproductive organs encodes LGR7-truncate. Deletion of exon 4 causes a reading frameshift in the LGR7-truncate transcript, the appearance of a premature stop codon, and results in a splice variant encoding a protein comprising the unique LDLa module of LGR7.…”