Identification of a gonadotropin-releasing hormone receptor orthologue in Caenorhabditis elegans.
BACKGROUND
The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs), but the GPCR(s) critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR) exist in C. elegans.


RESULTS
Our sequence analyses indicated the presence of two proteins in C. elegans, one of 401 amino acids [GenBank: NP_491453; WormBase: F54D7.3] and another of 379 amino acids [GenBank: NP_506566; WormBase: C15H11.2] with 46.9% and 44.7% nucleotide similarity to human GnRHR1 and GnRHR2, respectively. Like human GnRHR1, structural analysis of the C. elegans GnRHR1 orthologue (Ce-GnRHR) predicted a rhodopsin family member with 7 transmembrane domains, G protein coupling sites and phosphorylation sites for protein kinase C. Of the functionally important amino acids in human GnRHR1, 56% were conserved in the C. elegans orthologue. Ce-GnRHR was actively transcribed in adult worms and immunoanalyses using antibodies generated against both human and C. elegans GnRHR indicated the presence of a 46-kDa protein, the calculated molecular mass of the immature Ce-GnRHR. Ce-GnRHR staining was specifically localized to the germline, intestine and pharynx. In the germline and intestine, Ce-GnRHR was localized specifically to nuclei as revealed by colocalization with a DNA nuclear stain. However in the pharynx, Ce-GnRHR was localized to the myofilament lattice of the pharyngeal musculature, suggesting a functional role for Ce-GnRHR signaling in the coupling of food intake with reproduction. Phylogenetic analyses support an early evolutionary origin of GnRH-like receptors, as evidenced by the hypothesized grouping of Ce-GnRHR, vertebrate GnRHRs, a molluscan GnRHR, and the adipokinetic hormone receptors (AKHRs) and corazonin receptors of arthropods.


CONCLUSIONS
This is the first report of a GnRHR orthologue in C. elegans, which shares significant similarity with insect AKHRs. In vertebrates, GnRHRs are central components of the reproductive endocrine system, and the identification of a GnRHR orthologue in C. elegans suggests the potential use of C. elegans as a model system to study reproductive endocrinology.
Vadakkadath Meethal
Sivan
S
Section of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin and Geriatric Research, Education and Clinical Center, Veterans Administration Hospital, Madison, WI 53705, USA. svm@medicine.wisc.edu <svm@medicine.wisc.edu>
Gallego
Miguel J
MJ
Haasl
Ryan J
RJ
Petras
Stephen J
SJ
Sgro
Jean-Yves
JY
Atwood
Craig S
CS
D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D010802:Phylogeny; D011966:Receptors, LHRH / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
D029742:Caenorhabditis elegans Proteins; C484844:GNRHR protein, human; D011966:Receptors, LHRH