How is PAD4 activated?
Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation.
What does PAD4 do?
Peptidylarginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs) via PAD4-mediated histone citrullination.
What causes citrullination?
Histone citrullination occurs by enzymatic conversion of arginine residue to citrulline. This leads to chromatin relaxation and enables activation of transcription.
What happens NETosis?
NETosis is a unique form of cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space. The initial observation of NETosis placed the process within the context of the innate immune response to infections.
What is citrullination in rheumatoid arthritis?
Citrullination, the post-translational conversion of arginine to citrulline residues by peptidylarginine deiminase enzymes (PADs), is thought to be an essential contributor to the rheumatoid arthritis (RA) disease pathogenesis.
What is the function of citrullination?
Citrullination has an important role in the normal function of the immune system, skin keratinization, the insulation of neurons and the plasticity of the central nervous system including its essential role in gene regulation.
What is suicidal NETosis?
Suicidal NETosis was first described in a 2007 study that noted that the release of NETs resulted in neutrophil death through a different pathway than apoptosis or necrosis. In suicidal NETosis, the intracellular NET formation is followed by the rupture of the plasma membrane, releasing it into the extracellular space.
What is ACPA in rheumatoid arthritis?
In rheumatoid arthritis (RA), ACPA (anti-citrullinated protein/peptide antibody) is elevated with high specificity, and clinically, anti-CCP (cyclic citrullinated peptide) antibody is widely used for diagnosis of RA.
Is citrullination reversible?
In contrast to many other posttranslational modification (PTM), citrullination appears to be an irreversible process.
What is citrullination in RA?
Is citrullination a normal process?
Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells.