A pharmacological study of NLP-12 neuropeptide signaling in free-living and parasitic nematodes.
NLP-12a and b have been identified as cholecystokinin/sulfakinin-like neuropeptides in the free-living nematode Caenorhabditis elegans. They are suggested to play an important role in the regulation of digestive enzyme secretion and fat storage. This study reports on the identification and characterization of an NLP-12-like peptide precursor gene in the rat parasitic nematode Strongyloides ratti. The S. ratti NLP-12 peptides are able to activate both C. elegans CKR-2 receptor isoforms in a dose-dependent way with affinities in the same nanomolar range as the native C. elegans NLP-12 peptides. The C-terminal RPLQFamide sequence motif of the NLP-12 peptides is perfectly conserved between free-living and parasitic nematodes. Based on systemic amino acid replacements the Arg-, Leu- and Phe- residues appear to be critical for high-affinity receptor binding. Finally, a SAR analysis revealed the essential pharmacophore in C. elegans NLP-12b to be the pentapeptide RPLQFamide.
Functional Genomics and Proteomics Lab, K.U.Leuven, Naamsestraat 59, Leuven, Belgium. Lise.Peeters@bio.kuleuven.be
Lise
L
Peeters
Tom
T
Janssen
Wouter
W
De Haes
Isabel
I
Beets
Ellen
E
Meelkop
Warwick
W
Grant
Liliane
L
Schoofs
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009348:Nematoda / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017170:Strongyloides ratti / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D009479:Neuropeptides