Co-evolution of Ligand-Receptor Pairs in the Vasopressin/Oxytocin Superfamily of Bioactive Peptides

doi:10.1074/jbc.271.7.3619

Co-evolution of Ligand-Receptor Pairs in the Vasopressin/Oxytocin Superfamily of Bioactive Peptides (*)

From the (1)Departments of Experimental Zoology and
(2)Biochemistry, Graduate School of Neurosciences Amsterdam, Institute of Neuroscience, Vrije Universiteit, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands, the
(3)Ina Sue Perlmutter Laboratory, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, and the
(4)Institut für Zellbiochemie und Klinische Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany

^§To whom correspondence should be addressed:
Dept. of Experimental Zoology, Faculty of Biology, Vrije Universiteit, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
Tel.: 31-20-4447121: Fax: 31-20-4447123; revankes{at}bio.vu.nl.

↵^¶ Present address: Universität Potsdam & Deutsches Institut für Ernährungsforschung, Arthur-Scheunert-Allee 114-116, D-14558 Potsdam-Rehbrücke, Germany.

Abstract

In order to understand the molecular mechanisms that underlie the co-evolution of related yet functionally distinct peptide-receptor pairs, we study receptors for the vasopressin-related peptide Lys-conopressin in the mollusc Lymnaea stagnalis. In addition to a previously cloned Lys-conopressin receptor (LSCPR1), we have now identified a novel Lys-conopressin receptor subtype, named LSCPR2. The two receptors have a differential distribution in the reproductive organs and the brain, which suggests that they are involved in the control of distinct aspects of reproduction and mediate transmitter-like and/or modulatory effects of Lys-conopressin on different types of central neurons. In contrast to LSCPR1, LSCPR2 is maximally activated by both Lys-conopressin and Ile-conopressin, an oxytocin-like synthetic analog of Lys-conopressin. Together with a study of the phylogenetic relationships of Lys-conopressin receptors and their vertebrate counterparts, these data suggest that LSCPR2 represents an ancestral receptor to the vasopressin/oxytocin receptor family in the vertebrates. Based on our findings, we provide a theory of the molecular co-evolution of the functionally distinct ligand-receptor pairs of the vasopressin/oxytocin superfamily of bioactive peptides.

Footnotes

↵* This work was supported by Grant 805-26-203 (to R. E. v. K.) from the Foundation for Life Sciences (which is subsidized by the Netherlands Organization for Scientific Research), by European Community Grants 89300257/JUI and BIO2CT-CT93-0169), by Deutsche Forschungsgemeinschaft Grant SFB 232/B4, by a short term fellowship (to C. P. T.) from European Molecular Biology, and by International Human Frontier Science Program Grant RG-84/94 (to D. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(™)/EMBL Data Bank with accession number(s) U40491[GenBank].
↵¹ The abbreviations used are:

G protein

guanosine nucleotide binding protein

LSCPR

L. stagnalis conopressin receptor

TM

transmembrane domain

RT

reverse transcription

PCR

polymerase chain reaction

PAUP

phylogenetic analysis using parsimony.
↵²R. E. van Kesteren, unpublished results.
↵³Provided by K. A. Rice, Harvard University.
↵⁴R. E. van Kesteren, unpublished results.
↵⁵L. F. Kolakowski, Jr., and K. A. Rice, submitted for publication.
- Received September 15, 1995.