Identification of the Mouse T Cell ADP-Ribosylome Uncovers ARTC2.2 Mediated Regulation of CD73 by ADP-Ribosylation

• DOI: 10.3389/fimmu.2021.703719
• Publication Date: 2021-08-24T12:37:42Z
• Authors: Mario Leutert; Yinghui Duan; Riekje Winzer; Stephan Menzel; Eva Tolosa; Tim Magnus; Michael O. Hottiger; Friedrich Koch-Nolte; Björn Rissiek
• Keywords: ADP-ribosylation; Identification

Mouse T cells express the ecto-ADP-ribosyltransferase ARTC2.2, which can transfer ADP-ribose group of extracellular nicotinamide adenine dinucleotide (NAD + ) to arginine residues various cell surface proteins thereby influencing their function. Several targets such as P2X7, CD8a and CD25 have been identified, however a comprehensive mouse ADP-ribosylome analysis is currently missing. Using Af1521 macrodomain-based enrichment ADP-ribosylated peptides mass spectrometry, we identified 93 ADP-ribsoylated corresponding 67 distinct proteins, including known but also previously unknown CD73. We evaluated impact ADP-ribosylation on capability CD73 generate adenosine from monophosphate. Our results show that NAD reduces enzymatic activity HEK co-transfected with CD73/ARTC2.2. Importantly, significantly reduced WT CD8 compared ARTC2ko or treated an ARTC2.2-blocking nanobody. study provides list membrane serve for by ARTC2.2 whose function may be therefore affected ADP-ribosylation.