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Sci Rep. 2017 Nov 28;7(1):16477. doi: 10.1038/s41598-017-16613-w.

Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia.

Author information

1
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. b.rissiek@uke.de.
2
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland.
4
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Normandie Univ, UNIROUEN, INSERM, U1234, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.

Abstract

Mammalian ecto-ADP-ribosyltransferases (ecto-ARTs or also ARTCs) catalyze the ADP-ribosylation of cell surface proteins using extracellular nicotinamide adenine dinucleotide (NAD+) as substrate. By this post-translational protein modification, ecto-ARTs modulate the function of various target proteins. A functional role of ARTC2 has been demonstrated for peripheral immune cells such as T cells and macrophages. Yet, little is known about the role of ecto-ARTs in the central nervous system and on microglia. Here, we identified ARTC2.1 as the major ecto-ART expressed on murine microglia. ARTC2.1 expression was strongly upregulated on microglia upon co-stimulation with LPS and an ERK1/2 inhibitor or upon IFNβ stimulation. We identified several target proteins modified by ARTC2.1 on microglia with a recently developed mass spectrometry approach, including two receptors for immunoglobulin G (IgG), FcγR1 and FcγR2B. Both proteins were verified as targets of ARTC2.1 in vitro using a radiolabeling assay with 32P-NAD+ as substrate. Moreover, ADP-ribosylation of both targets strongly inhibited their capacity to bind IgG. In concordance, ARTC2.1 induction in WT microglia and subsequent cell surface ADP-ribosylation significantly reduced the phagocytosis of IgG-coated latex beads, which was unimpaired in NAD+/DTT treated microglia from ARTC2.1-/- mice. Hence, induction of ARTC2.1 expression under inflammatory conditions, and subsequent ADP-ribosylation of cell surface target proteins could represent a hitherto unnoticed mechanism to regulate the immune response of murine microglia.

PMID:
29184112
PMCID:
PMC5705771
DOI:
10.1038/s41598-017-16613-w
[Indexed for MEDLINE]
Free PMC Article

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