An evolutionary comparison of leucine-rich repeat containing G protein-coupled receptors reveals a novel LGR subtype

Abstract

Leucine-rich repeat containing G protein-coupled receptors or LGRs are receptors with important functions in development and reproduction. Belonging to this evolutionarily conserved group of receptors are the well-studied glycoprotein hormone receptors and relaxin receptors in mammals, as well as the bursicon receptor, which triggers cuticle hardening and tanning in freshly enclosed insects. In this study, the numerous LGR sequences in different animal phyla are analyzed and compared. Based on these data a phylogenetic tree was generated. This information sheds new light on structural and evolutionary aspects regarding this receptor group. Apart from vertebrates and insects, LGRs are also present in early chordates (Urochordata, Cephalochordata and Hyperoartia) and other arthropods (Arachnida and Branchiopoda) as well as in Mollusca, Echinodermata, Hemichordata, Nematoda, and even in ancient animal life forms, such as Cnidaria and Placozoa. Three distinct types of LGR exist, distinguishable by their number of leucine-rich repeats (LRRs), their type-specific hinge region and the presence or absence of an LDLa motif. Type C LGRs containing only one LDLa (C1 subtype) appear to be present in nearly all animal phyla. We here describe a second subtype, C2, containing multiple LDLa motifs, which was discovered in echinoderms, mollusks and in one insect species (Pediculus humanis corporis). In addition, eight putative LGRs can be predicted from the genome data of the placozoan species Trichoplax adhaerens. They may represent an ancient form of the LGRs, however, more genomic data will be required to confirm this hypothesis.

A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3

“…The relaxin receptor Lgr3 mediates Dilp8-induced homeostatic control Dilp8 bears homology to the human relaxin peptides (12,25,26). Therefore, we investigated the role for the two fly relaxin receptors encoded by the orphan leucine-rich repeatcontaining G-protein coupled receptors (LGRs), Lgr3 (CG31096) and Lgr4 (CG34411) (27).…”

The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

“…This LRR region is flanked by N-terminal and C-terminal cap modules. The eight LGRs can be further subdivided into class A, B, and C receptors (Van Loy et al 2008;Van Hiel et al 2012). A-type receptors contain seven to nine LRRs and a long Hinge region connecting the LRR region with the 7TM domain.…”

Lgr proteins in epithelial stem cell biology

“…The Lgr family proteins can be subdivided into three main groups (A, B and C), according to the relative abundance of LRRs within their ectodomain, together with the presence or absence of a low-density lipoprotein receptor class A domain (LDLa) and the structure of a hinge region connecting the 7TM region to the LRR domain (Kajava, 1998;Van Hiel et al, 2012) (Fig. 1B).…”

“…It was first identified as a highly related subclass of the glycoprotein hormone receptor GPCR family during EST database homology searches in the late 1990s (Hsu et al, 2000;Hsu et al, 1998;McDonald et al, 1998). Subsequent phylogenetic analyses revealed the existence of Lgr4-6 homologs throughout the entire animal kingdom, including ancient life forms such as Cnidaria and Placozoa (Luo and Hsueh, 2006;Van Hiel et al, 2012). This reflects both their common ancient origins and their likely functional importance.…”