The mono-ADP-ribosyltransferase ARTD10 regulates the voltage-gated K+ channel Kv1.1 through protein kinase C delta

BMC Biology

Daniel Komnig¹  Björn H. Falkenburger²  Patricia Korn³  Bernhard Lüscher³  Arno Classen⁴  Carsten Bolm⁴  Stefan Gründer⁵  Dominik Wiemuth⁵  Azadeh Nikouee⁵  Yuemin Tian⁵  Priyanka Tripathi⁶ 

[1] Department of Neurology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany;JARA-Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich, Jülich, Germany;Department of Neurology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany;JARA-Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich, Jülich, Germany;Present address: Department of Neurology, Dresden University Medical Center, Fetscherstraße 74, 01307, Dresden, Germany;Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany;Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056, Aachen, Germany;Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany;Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany;Present address: Institute of Neuropathology, RWTH Aachen University Medical School, Pauwelsstrasse 30, 52074, Aachen, Germany;

关键词: Ion channel;    Potassium channel;    ADP ribosylation;    Posttranslational modification;    ADP ribosyltransferase;    Protein kinase C delta;    PARP10;   

DOI  :  10.1186/s12915-020-00878-1

来源: Springer

【 摘 要 】

BackgroundADP-ribosylation is a ubiquitous post-translational modification that involves both mono- and poly-ADP-ribosylation. ARTD10, also known as PARP10, mediates mono-ADP-ribosylation (MARylation) of substrate proteins. A previous screen identified protein kinase C delta (PKCδ) as a potential ARTD10 substrate, among several other kinases. The voltage-gated K+ channel Kv1.1 constitutes one of the dominant Kv channels in neurons of the central nervous system and the inactivation properties of Kv1.1 are modulated by PKC. In this study, we addressed the role of ARTD10-PKCδ as a regulator of Kv1.1.ResultsWe found that ARTD10 inhibited PKCδ, which increased Kv1.1 current amplitude and the proportion of the inactivating current component in HeLa cells, indicating that ARTD10 regulates Kv1.1 in living cells. An inhibitor of ARTD10, OUL35, significantly decreased peak amplitude together with the proportion of the inactivating current component of Kv1.1-containing channels in primary hippocampal neurons, demonstrating that the ARTD10-PKCδ signaling cascade regulates native Kv1.1. Moreover, we show that the pharmacological blockade of ARTD10 increases excitability of hippocampal neurons.ConclusionsOur results, for the first time, suggest that MARylation by ARTD10 controls neuronal excitability.

【 授权许可】

CC BY