Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans
Name
vanBael2018.pdf
Description
Accepted version
Size
2.51 MB
Format
Adobe PDF
Checksum (MD5)
498077b58fbcd58d449676ce9f0c3ed3
Author(s)
Van Bael, Sven
Watteyne, Jan
Boonen, Kurt
De Haes, Wouter
Menschaert, Gerben
Ringstad, Niels
Horvitz, Howard Robert
Schoofs, Liliane
Husson, Steven J.
Temmerman, Liesbet
Date Issued
February 2018
Journal
Journal of Biological Chemistry
Publisher
Elsevier BV
Citation
Van Bael, Sven et al. "Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans." Journal of Biological Chemistry 293, 16 (February 2018): 6052–6063. © 2018 The American Society for Biochemistry and Molecular Biology, Inc.
Version
Author's final manuscript
Abstract
Neuropeptides constitute a vast and functionally diverse family of neurochemical signaling molecules and are widely involved in the regulation of various physiological processes. The nematode Caenorhabditis elegans is well-suited for the study of neuropeptide biochemistry and function, as neuropeptide biosynthesis enzymes are not essential for C. elegans viability. This permits the study of neuropeptide biosynthesis in mutants lacking certain neuropeptide-processing enzymes. Mass spectrometry has been used to study the effects of proprotein convertase and carboxypeptidase mutations on proteolytic processing of neuropeptide precursors and on the peptidome in C. elegans. However, the enzymes required for the last step in the production of many bioactive peptides, the carboxyl-terminal amidation reaction, have not been characterized in this manner. Here, we describe three genes that encode homologs of neuropeptide amidation enzymes in C. elegans and used tandem LC-MS to compare neuropeptides in WT animals with those in newly generated mutants for these putative amidation enzymes. We report that mutants lacking both a functional peptidylglycine -hydroxylating monooxygenase and a peptidylglycine -amidating monooxygenase had a severely altered neuropeptide profile and also a decreased number of offspring. Interestingly, single mutants of the amidation enzymes still expressed some fully processed amidated neuropeptides, indicating the existence of a redundant amidation mechanism in C. elegans. All MS data are available via ProteomeXchange with the identifier PXD008942. In summary, the key steps in neuropeptide processing in C. elegans seem to be executed by redundant enzymes, and loss of these enzymes severely affects brood size, supporting the need of amidated peptides for C. elegans reproduction.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912480/
