Functions of a GnRH receptor heterodimer of the ascidian, Ciona intestinalis.
Gonadotropin-releasing hormone (GnRH) is a ten-amino acid peptide hormone that plays pivotal roles in reproduction in vertebrates and octopus. Recently, six GnRH forms (t-GnRH-3-8) and four GnRH receptor subtypes (Ci-GnRHR-1-4) were identified in the protochordate, Ciona intestinalis. In this study, we show the functional modulation of Ci-GnRHR-1 via heterodimerization with the orphan receptor subtype, Ci-GnRHR-4. The dimerization between Ci-GnRHR-1 and R-4 was detected by co-immunoprecipitation and immunoblot analysis. Binding assays confirmed the binding of t-GnRHs to Ci-GnRHR-1 but not to R-4, and verified no alternation in ligand-binding affinity between Ci-GnRHR-1 homodimer and Ci-GnRHRI&4 heterodimer. The heterodimer was found to stimulate the elevation of intracellular calcium, time-extension of ERK phosphorylation, and up-regulation of cell proliferation, all in a ligand specific manner, compared with the Ci-GnRHR-1 homodimer. In combination, these results indicated that Ci-GnRHR-4 is not an inactive receptor, but a modulatory factor for Ci-GnRHR-1 in C. intestinalis.
Sakai
T
T
Suntory Institute for Bioorganic Research, Osaka, Japan. sakai@sunbor.or.jp
Aoyama
M
M
Kusakabe
T
T
Tsuda
M
M
Satake
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002938:Ciona intestinalis / Q000166:cytology / Q000378:metabolism*; D019281:Dimerization; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D020836:Protein Structure, Quaternary; D011966:Receptors, LHRH / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium