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Complement component C4-like protein in Atlantic cod (Gadus morhua L.) - Detection in ontogeny and identification of post-translational deimination in serum and extracellular vesicles

Lange, Sigrun, Kraev, Igor, Magnadóttir, Bergljót, Dodds, Alister W.
Developmental and comparative immunology 2019 v.101 pp. 103437
Gadus morhua, antibodies, arginine, blood serum, brain, citrulline, complement, early development, eyes, immunohistochemistry, kidneys, larvae, lectins, liver, mucosa, mucus, muscles, neurons, ontogeny, protein structure, spinal cord
The complement system is a critical part of teleost immune defences, with complement component C4 forming part of the classical and lectin pathways. Cod C4-like protein was isolated from plasma, specific antibodies generated and C4-like protein was assessed in cod sera, mucus and in extracellular vesicles (EVs) from serum and mucus. Higher levels of C4-like protein were detected in serum- than mucus-derived EVs. Post-translational deimination, caused by conversion of arginine into citrulline, can affect protein structure and function. Here we detected deiminated forms of C4-like protein in cod serum and at lower levels in mucus. C4-like protein was also found in deiminated form at low levels in EVs from both serum and mucus. C4-like protein was assessed by immunohistochemistry in cod larvae and detected in a range of organs including in liver, kidney, gut, muscle, skin and mucus, as well as in neuronal tissues of the brain, spinal cord and eye. This abundance of C4-like protein during early development may indicate roles in tissue remodelling, in addition to immune defences. The presence of deiminated C4-like protein in serum and mucosa, as well as in EVs, may suggest C4 protein moonlighting via post-translational deimination.