Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)-Novel insights into camelid immunity.
Adaptive immunity
Adiponectin
Complement
Histone
Immunoglobulin
Innate immunity
Llama (Lama glama)
Metabolism
Nanobodies
Peptidylarginine deiminases (PADs)
Protein deimination
extracellular vesicles (EVs)
Journal
Molecular immunology
ISSN: 1872-9142
Titre abrégé: Mol Immunol
Pays: England
ID NLM: 7905289
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
03
07
2019
revised:
05
10
2019
accepted:
23
10
2019
pubmed:
17
11
2019
medline:
10
4
2020
entrez:
17
11
2019
Statut:
ppublish
Résumé
Peptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which post-translationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also allows for protein moonlighting. Furthermore, PADs have been found to be a phylogenetically conserved regulator for extracellular vesicle (EVs) release. EVs are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material. In this study, post-translationally deiminated proteins in serum and serum-EVs are described for the first time in camelids, using the llama (Lama glama L. 1758) as a model animal. We report a poly-dispersed population of llama serum EVs, positive for phylogenetically conserved EV-specific markers and characterised by TEM. In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. In serum, 60 deiminated proteins were identified that were not in EVs, and 25 deiminated proteins were found to be unique to EVs, with 43 shared deiminated protein hits between both serum and EVs. Deiminated histone H3, a marker of neutrophil extracellular trap formation, was also detected in llama serum. PAD homologues were identified in llama serum by Western blotting, via cross reaction with human PAD antibodies, and detected at an expected 70 kDa size. This is the first report of deiminated proteins in serum and EVs of a camelid species, highlighting a hitherto unrecognized post-translational modification in key immune and metabolic proteins in camelids, which may be translatable to and inform a range of human metabolic and inflammatory pathologies.
Identifiants
pubmed: 31733447
pii: S0161-5890(19)30483-3
doi: 10.1016/j.molimm.2019.10.017
pmc: PMC7112542
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
37-53Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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