Menzel, Stephan, Rissiek, Björn, Bannas, Peter, Jakoby, Thomas, Miksiewicz, Maria, Schwarz, Nicole, Nissen, Marion, Haag, Friedrich, Tholey, Andreas and Koch-Nolte, Friedrich (2015) Nucleotide-Induced Membrane-Proximal Proteolysis Controls the Substrate Specificity of T Cell Ecto–ADP-Ribosyltransferase ARTC2.2. The Journal of Immunology, 195 (5). pp. 2057-2066. DOI 10.4049/jimmunol.1401677.

Full text not available from this repository.

Abstract

ARTC2.2 is a toxin-related, GPI-anchored ADP-ribosyltransferase expressed by murine T cells. In response to NAD(+) released from damaged cells during inflammation, ARTC2.2 ADP-ribosylates and thereby gates the P2X7 ion channel. This induces ectodomain shedding of metalloprotease-sensitive cell surface proteins. In this study, we show that ARTC2.2 itself is a target for P2X7-triggered ectodomain shedding. We identify the metalloprotease cleavage site 3 aa upstream of the predicted GPI anchor attachment site of ARTC2.2. Intravenous injection of NAD(+) increased the level of enzymatically active ARTC2.2 in serum, indicating that this mechanism is operative also under inflammatory conditions in vivo. Radio-ADP-ribosylation assays reveal that shedding refocuses the target specificity of ARTC2.2 from membrane proteins to secretory proteins. Our results uncover nucleotide-induced membrane-proximal proteolysis as a regulatory mechanism to control the substrate specificity of ARTC2.2.

Document Type:	Article
Research affiliation:	Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	Yes
Publisher:	The American Association of Immunologists
Date Deposited:	01 Feb 2018 12:46
Last Modified:	26 Apr 2019 11:03
URI:	https://oceanrep.geomar.de/id/eprint/41791

Actions (login required)

View Item