A neuromedin-pyrokinin-like neuropeptide signaling system in Caenorhabditis elegans.
Neuromedin U (NMU) in vertebrates is a structurally highly conserved neuropeptide of which highest levels are found in the pituitary and gastrointestinal tract. In Drosophila, two neuropeptide genes encoding pyrokinins (PKs), capability (capa) and hugin, are possible insect homologs of vertebrate NMU. Here, the ligand for an orphan G protein-coupled receptor in the nematode Caenorhabditis elegans (Ce-PK-R) was found using a bioinformatics approach. After cloning and expressing Ce-PK-R in HEK293T cells, we found that it was activated by a neuropeptide from the C. elegans NLP-44 precursor (EC(50)=18nM). This neuropeptide precursor is reminiscent of insect CAPA precursors since it encodes a PK-like peptide and two periviscerokinin-like peptides (PVKs). Analogous to CAPA peptides in insects and NMUs in vertebrates, whole mount immunostaining in C. elegans revealed that the CAPA precursor is expressed in the nervous system. The present data also suggest that the ancestral CAPA precursor was already present in the common ancestor of Protostomians and Deuterostomians and that it might have been duplicated into CAPA and HUGIN in insects. In vertebrates, NMU is the putative homolog of a protostomian CAPA-PK.
Lindemans
Marleen
M
Functional Genomics and Proteomics Research Unit, Katholieke Universiteit Leuven, Naamsestraat 59, Leuven, Belgium. marleen.lindemans@bio.kuleuven.be
Janssen
Tom
T
Husson
Steven J
SJ
Meelkop
Ellen
E
Temmerman
Liesbet
L
Clynen
Elke
E
Mertens
Inge
I
Schoofs
Liliane
L
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; C079229:pyrokinin; C538749:pyrokinin receptor, C elegans; C056900:neuromedin U