Impaired processing of FLP and NLP peptides in carboxypeptidase E (EGL-21)-deficient Caenorhabditis elegans as analyzed by mass spectrometry.
Biologically active peptides are synthesized from inactive pre-proproteins or peptide precursors by the sequential actions of processing enzymes. Proprotein convertases cleave the precursor at pairs of basic amino acids, which are then removed from the carboxyl terminus of the generated fragments by a specific carboxypeptidase. Caenorhabditis elegans strains lacking proprotein convertase EGL-3 display a severely impaired neuropeptide profile (Husson et al. 2006, J. Neurochem.98, 1999-2012). In the present study, we examined the role of the C. elegans carboxypeptidase E orthologue EGL-21 in the processing of peptide precursors. More than 100 carboxy-terminally extended neuropeptides were detected in egl-21 mutant strains. These findings suggest that EGL-21 is a major carboxypeptidase involved in the processing of FMRFamide-like peptide (FLP) precursors and neuropeptide-like protein (NLP) precursors. The impaired peptide profile of egl-3 and egl-21 mutants is reflected in some similar phenotypes. They both share a severe widening of the intestinal lumen, locomotion defects, and retention of embryos. In addition, egl-3 animals have decreased intestinal fat content. Taken together, these results suggest that EGL-3 and EGL-21 are key enzymes for the proper processing of neuropeptides that control egg-laying, locomotion, fat storage and the nutritional status.
Husson
Steven J
SJ
Functional Genomics and Proteomics Unit, Department of Biology, Katholieke Universiteit Leuven, Leuven, Belgium. steven.husson@bio.kuleuven.be
Janssen
Tom
T
Baggerman
Geert
G
Bogert
Brigitte
B
Kahn-Kirby
Amanda H
AH
Ashrafi
Kaveh
K
Schoofs
Liliane
L
D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D043423:Carboxypeptidase H / Q000235:genetics / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D009479:Neuropeptides / Q000502:physiology*; D010078:Oxazines; D010455:Peptides / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D029742:Caenorhabditis elegans Proteins; C114560:Flp-1 protein, C elegans; D009479:Neuropeptides; D010078:Oxazines; D010455:Peptides; D043423:Carboxypeptidase H; C044808:nile red