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Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis
Many secreted peptides used for cell–cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529398/ https://www.ncbi.nlm.nih.gov/pubmed/30879092 http://dx.doi.org/10.1007/s00018-019-03065-w |
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author | Kumar, Dhivya Mains, Richard E. Eipper, Betty A. King, Stephen M. |
author_facet | Kumar, Dhivya Mains, Richard E. Eipper, Betty A. King, Stephen M. |
author_sort | Kumar, Dhivya |
collection | PubMed |
description | Many secreted peptides used for cell–cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Recent studies have revealed that in addition to playing a key role in peptidergic signaling, PAM also regulates ciliogenesis in vertebrates, planaria and chlorophyte algae, and is required for the stability of actin-based microvilli. Here we briefly introduce the basic principles involved in ciliogenesis, the sequential reactions catalyzed by PAM and the trafficking of PAM through the secretory and endocytic pathways. We then discuss the multi-faceted roles this enzyme plays in the formation and maintenance of cytoskeleton-based cellular protrusions and propose models for how PAM protein and amidating activity might contribute to ciliogenesis. Finally, we consider why some ciliated organisms lack PAM, and discuss the potential ramifications of ciliary localized PAM for the endocrine features commonly observed in patients with ciliopathies. |
format | Online Article Text |
id | pubmed-6529398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-65293982019-06-07 Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis Kumar, Dhivya Mains, Richard E. Eipper, Betty A. King, Stephen M. Cell Mol Life Sci Review Many secreted peptides used for cell–cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Recent studies have revealed that in addition to playing a key role in peptidergic signaling, PAM also regulates ciliogenesis in vertebrates, planaria and chlorophyte algae, and is required for the stability of actin-based microvilli. Here we briefly introduce the basic principles involved in ciliogenesis, the sequential reactions catalyzed by PAM and the trafficking of PAM through the secretory and endocytic pathways. We then discuss the multi-faceted roles this enzyme plays in the formation and maintenance of cytoskeleton-based cellular protrusions and propose models for how PAM protein and amidating activity might contribute to ciliogenesis. Finally, we consider why some ciliated organisms lack PAM, and discuss the potential ramifications of ciliary localized PAM for the endocrine features commonly observed in patients with ciliopathies. Springer International Publishing 2019-03-16 2019 /pmc/articles/PMC6529398/ /pubmed/30879092 http://dx.doi.org/10.1007/s00018-019-03065-w Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Kumar, Dhivya Mains, Richard E. Eipper, Betty A. King, Stephen M. Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
title | Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
title_full | Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
title_fullStr | Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
title_full_unstemmed | Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
title_short | Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
title_sort | ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529398/ https://www.ncbi.nlm.nih.gov/pubmed/30879092 http://dx.doi.org/10.1007/s00018-019-03065-w |
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