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Cell Rep. 2018 Aug 14;24(7):1916-1929.e5. doi: 10.1016/j.celrep.2018.07.048.

Proteomic Characterization of the Heart and Skeletal Muscle Reveals Widespread Arginine ADP-Ribosylation by the ARTC1 Ectoenzyme.

Author information

1
Department of Molecular Mechanisms of Disease, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Molecular Life Science PhD Program of the Life Science Zurich Graduate School, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
2
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
3
Functional Genomics Center Zurich, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
4
Department of Biochemistry and Molecular Biophysics, Kansas State University, 141 Chalmers Hall, Manhattan, KS 66506, USA.
5
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: nolte@uke.de.
6
Department of Molecular Mechanisms of Disease, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: michael.hottiger@dmmd.uzh.ch.

Abstract

The clostridium-like ecto-ADP-ribosyltransferase ARTC1 is expressed in a highly restricted manner in skeletal muscle and heart tissue. Although ARTC1 is well studied, the identification of ARTC1 targets in vivo and subsequent characterization of ARTC1-regulated cellular processes on the proteome level have been challenging and only a few ARTC1-ADP-ribosylated targets are known. Applying our recently developed mass spectrometry-based workflow to C2C12 myotubes and to skeletal muscle and heart tissues from wild-type mice, we identify hundreds of ARTC1-ADP-ribosylated proteins whose modifications are absent in the ADP-ribosylome of ARTC1-deficient mice. These proteins are ADP-ribosylated on arginine residues and mainly located on the cell surface or in the extracellular space. They are associated with signal transduction, transmembrane transport, and muscle function. Validation of hemopexin (HPX) as a ARTC1-target protein confirmed the functional importance of ARTC1-mediated extracellular arginine ADP-ribosylation at the systems level.

KEYWORDS:

ADP-ribosylation; ARTC1; C2C12; arginine modification; heart; hemopexin; mass spectrometry; muscle; post-translational modification; proteomics

PMID:
30110646
DOI:
10.1016/j.celrep.2018.07.048
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