Post-translational protein deimination signatures and extracellular vesicles (EVs) in the Atlantic horseshoe crab (Limulus polyphemus). (September 2020)

• Record Type: Journal Article
• Authors: Bowden, Timothy J.; Kraev, Igor; Lange, Sigrun
• Is Part Of: Developmental and comparative immunology. Volume 110(2020)
• Publication Date: 2020-09
• Subjects: Peptidylarginine deiminases (PADs) -- Protein deimination -- Horseshoe crab (Limulus polyphemus) -- Extracellular vesicles (EVs) -- Innate immunity -- CRP -- Complement; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2020.103714
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: The horseshoe crab is a living fossil and a species of marine arthropod with unusual immune system properties which are also exploited commercially. Given its ancient status dating to the Ordovician period (450 million years ago), its standing in phylogeny and unusual immunological characteristics, the horseshoe crab may hold valuable information for comparative immunology studies. Peptidylarginine deiminases (PADs) are calcium dependent enzymes that are phylogenetically conserved and cause protein deimination via conversion of arginine to citrulline. This post-translational modification can lead to structural and functional protein changes contributing to protein moonlighting in health and disease. PAD-mediated regulation of extracellular vesicle (EV) release, a critical component of cellular communication, has furthermore been identified to be a phylogenetically conserved mechanism. PADs, protein deimination and EVs have hitherto not been studied in the horseshoe crab and were assessed in the current study. Horseshoe crab haemolymph serum-EVs were found to be a poly-dispersed population in the 20–400 nm size range, with the majority of EVs falling within 40–123 nm. Key immune proteins were identified to be post-translationally deiminated in horseshoe crab haemolymph serum, providing insights into protein moonlighting function of Limulus and phylogenetically conserved immune proteins. KEGG (Kyoto encyclopaedia of genes and genomes) and GO (gene ontology) enrichment analysis of deiminated proteins identified in Limulus revealed KEGG pathways relating to complement and coagulation pathways, Staphylococcus aureus infection, glycolysis/gluconeogenesis and carbon metabolism, while GO pathways of biological and molecular pathways related to a range of immune and metabolic functions, as well as developmental processes. The characterisation of EVs, and post-translational deimination signatures, revealed here in horseshoe crab, contributes to current understanding of protein moonlighting functions and EV-mediated communication in this ancient arthropod and throughout phylogeny. Graphical abstract: Image 1 Highlights: PAD and protein deimination signatures were identified in horseshoe crab ( Limulus polyphemus ). Extracellular vesicles (EVs) were profiled in horseshoe crab. Deiminated proteins identified in Limulus are involved in key immune and metabolic functions. Protein deimination contributes to protein moonlighting in phylogenetically conserved immune and metabolic proteins.