Co-evolution of ligand-receptor pairs in the vasopressin/oxytocin superfamily of bioactive peptides.
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.
van Kesteren
R E
RE
Department of Experimental Zoology, Graduate School of Neurosciences Amsterdam, Institute of Neuroscience, Vrije Universiteit, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
Tensen
C P
CP
Smit
A B
AB
van Minnen
J
J
Kolakowski
L F
LF
Meyerhof
W
W
Richter
D
D
van Heerikhuizen
H
H
Vreugdenhil
E
E
Geraerts
W P
WP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017931:DNA Primers; D005260:Female; D017952:Ganglia, Invertebrate / Q000378:metabolism; D008195:Lymnaea; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D009928:Organ Specificity; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014667:Vasopressins / Q000494:pharmacology; D014982:Xenopus laevis
D017931:DNA Primers; C096468:LSCPR1 protein, Lymnaea stagnalis; C490751:LSCPR2 protein, Lymnaea stagnalis; D008565:Membrane Proteins; D017483:Receptors, Vasopressin; D014667:Vasopressins; C076621:conopressin G; D010121:Oxytocin