Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans
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 neuropepti...
| Main Authors: | , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
|
| Online Access: | https://hdl.handle.net/1721.1/129427 |
| _version_ | 1811079422293311488 |
|---|---|
| author | Van Bael, Sven Watteyne, Jan Boonen, Kurt De Haes, Wouter Menschaert, Gerben Ringstad, Niels Horvitz, Howard Robert Schoofs, Liliane Husson, Steven J. Temmerman, Liesbet |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Van Bael, Sven Watteyne, Jan Boonen, Kurt De Haes, Wouter Menschaert, Gerben Ringstad, Niels Horvitz, Howard Robert Schoofs, Liliane Husson, Steven J. Temmerman, Liesbet |
| author_sort | Van Bael, Sven |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:14:46Z |
| format | Article |
| id | mit-1721.1/129427 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:14:46Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1294272022-10-01T02:19:59Z Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans Van Bael, Sven Watteyne, Jan Boonen, Kurt De Haes, Wouter Menschaert, Gerben Ringstad, Niels Horvitz, Howard Robert Schoofs, Liliane Husson, Steven J. Temmerman, Liesbet Massachusetts Institute of Technology. Department of Biology 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. 2021-01-14T20:59:27Z 2021-01-14T20:59:27Z 2018-02 2020-04-24T12:14:46Z Article http://purl.org/eprint/type/JournalArticle 0021-9258 1083-351X https://hdl.handle.net/1721.1/129427 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. en https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912480/ Journal of Biological Chemistry Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier BV MIT web domain |
| spellingShingle | Van Bael, Sven Watteyne, Jan Boonen, Kurt De Haes, Wouter Menschaert, Gerben Ringstad, Niels Horvitz, Howard Robert Schoofs, Liliane Husson, Steven J. Temmerman, Liesbet Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans |
| title | Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans |
| title_full | Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans |
| title_fullStr | Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans |
| title_full_unstemmed | Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans |
| title_short | Mass spectrometric evidence for neuropeptide-amidating enzymes inCaenorhabditis elegans |
| title_sort | mass spectrometric evidence for neuropeptide amidating enzymes incaenorhabditis elegans |
| url | https://hdl.handle.net/1721.1/129427 |
| work_keys_str_mv | AT vanbaelsven massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT watteynejan massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT boonenkurt massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT dehaeswouter massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT menschaertgerben massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT ringstadniels massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT horvitzhowardrobert massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT schoofsliliane massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT hussonstevenj massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans AT temmermanliesbet massspectrometricevidenceforneuropeptideamidatingenzymesincaenorhabditiselegans |