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

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 targ...

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Auteurs principaux:	Björn Rissiek, Stephan Menzel, Mario Leutert, Maike Cordes, Sarah Behr, Larissa Jank, Peter Ludewig, Mathias Gelderblom, Anne Rissiek, Sahil Adriouch, Friedrich Haag, Michael O. Hottiger, Friedrich Koch-Nolte, Tim Magnus
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2017
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/b1ae8aec05a84e56935b6f2b9f614cd9
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spelling	oai:doaj.org-article:b1ae8aec05a84e56935b6f2b9f614cd92021-12-02T11:40:50ZEcto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia10.1038/s41598-017-16613-w2045-2322https://doaj.org/article/b1ae8aec05a84e56935b6f2b9f614cd92017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16613-whttps://doaj.org/toc/2045-2322Abstract 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.Björn RissiekStephan MenzelMario LeutertMaike CordesSarah BehrLarissa JankPeter LudewigMathias GelderblomAnne RissiekSahil AdriouchFriedrich HaagMichael O. HottigerFriedrich Koch-NolteTim MagnusNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Björn Rissiek Stephan Menzel Mario Leutert Maike Cordes Sarah Behr Larissa Jank Peter Ludewig Mathias Gelderblom Anne Rissiek Sahil Adriouch Friedrich Haag Michael O. Hottiger Friedrich Koch-Nolte Tim Magnus Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia
description	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.
format	article
author	Björn Rissiek Stephan Menzel Mario Leutert Maike Cordes Sarah Behr Larissa Jank Peter Ludewig Mathias Gelderblom Anne Rissiek Sahil Adriouch Friedrich Haag Michael O. Hottiger Friedrich Koch-Nolte Tim Magnus
author_facet	Björn Rissiek Stephan Menzel Mario Leutert Maike Cordes Sarah Behr Larissa Jank Peter Ludewig Mathias Gelderblom Anne Rissiek Sahil Adriouch Friedrich Haag Michael O. Hottiger Friedrich Koch-Nolte Tim Magnus
author_sort	Björn Rissiek
title	Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia
title_short	Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia
title_full	Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia
title_fullStr	Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia
title_full_unstemmed	Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia
title_sort	ecto-adp-ribosyltransferase artc2.1 functionally modulates fcγr1 and fcγr2b on murine microglia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b1ae8aec05a84e56935b6f2b9f614cd9
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Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcγR1 and FcγR2B on murine microglia

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