Deiminated proteins and extracellular vesicles - Novel serum biomarkers in whales and orca

We report for the first time deimination of key immune and metabolic proteins in whale and orca sera, characterise serum-derived Extracellular vesicles and assess extracellular vesicle -mediated export of key miRs involved in immune responses and metabolism

Bergljót Magnadóttir; Pinar Uysal-Onganer; Igor Kraev; Vilhjálmur Svansson; Polly Hayes; Sigrun Lange

2020

Scholarcy highlights

  • Peptidylarginine deiminases are phylogenetically conserved calcium-dependent enzymes which post-translationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural protein changes
  • 3.1 Extracellular vesicles profile analysis of whale and orca sera EVs from whale and orca sera were characterised by nanoparticle tracking analysis for size profiling, by morphological analysis using transmission electron microscopy and by Western blotting using EV-specific markers
  • NTA profiles of EVs revealed poly-dispersed EV populations which overall fell within a range of approximately 50 – 500 nm, albeit with some variation between the 5 cetaceans
  • Western blotting confirmed that the EVs were positive for the EV-specific markers CD63 and Flot-1, which have been shown to be phylogenetically conserved from fish to mammals
  • The findings presented here unravel novel aspects of post-translational deimination in key proteins of metabolism, innate and adaptive immunity in these sea mammals
  • PAD homologues were identified in whale sera by Western blotting via cross reaction with human PAD2 and PAD3
  • Selected deiminated protein candidates, based on Journal Pre-proof identification from the species-specific search for the individual cetaceans under study, which are involved in immune, nuclear and metabolic functions are discussed below in relation to roles in physiology and pathology: Adiponectin was identified to be deiminated in orca only and is in human the most abundant secreted adipokine with pleiotropic roles in physiological and pathophysiological processes

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