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Article

CK1BP Reduces α-Synuclein Oligomerization and Aggregation Independent of Serine 129 Phosphorylation

by 1, 2, 3, 1,4,*,† and 1,4,*,†
1
Department of Neurology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
2
Neurobiological Research, University Medical Center and Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany
3
Institute for Occupational, Social and Environmental Medicine, RWTH Aachen University, 52074 Aachen, Germany
4
JARA-BRAIN Institute of Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, 52074 Aachen, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Lucilla Parnetti and Giovanni Bellomo
Cells 2021, 10(11), 2830; https://doi.org/10.3390/cells10112830
Received: 29 September 2021 / Revised: 9 October 2021 / Accepted: 15 October 2021 / Published: 21 October 2021
The pathological accumulation of α-Synuclein (α-Syn) is the hallmark of neurodegenerative α-synucleinopathies, including Parkinsons’s disease (PD). In contrast to the mostly non-phosphorylated soluble α-Syn, aggregated α-Syn is usually phosphorylated at serine 129 (S129). Therefore, S129-phosphorylation is suspected to interfere with α-Syn aggregation. Among other kinases, protein kinase CK1 (CK1) is known to phosphorylate α-Syn at S129. We overexpressed CK1 binding protein (CK1BP) to inhibit CK1 kinase activity. Using Bimolecular Fluorescence Complementation (BiFC) in combination with biochemical methods, we monitored the S129 phosphorylation and oligomerization of α-Syn in HEK293T cells. We found that CK1BP reduced the overall protein levels of α-Syn. Moreover, CK1BP concomitantly reduced S129 phosphorylation, oligomerization and the amount of insoluble α-Syn. Analyzing different α-Syn variants including S129 mutations, we show that the effects of CK1BP on α-Syn accumulation were independent of S129 phosphorylation. Further analysis of an aggregating polyglutamine (polyQ) protein confirmed a phosphorylation-independent decrease in aggregation. Our results imply that the inhibition of CK1 activity by CK1BP might exert beneficial effects on NDDs in general. Accordingly, CK1BP represents a promising target for the rational design of therapeutic approaches to cease or at least delay the progression of α-synucleinopathies. View Full-Text
Keywords: CK1BP; CK1; α-Synuclein; α-Synuclein oligomerization; α-Synuclein aggregation; Parkinson’s disease; serine 129 phosphorylation; BiFC CK1BP; CK1; α-Synuclein; α-Synuclein oligomerization; α-Synuclein aggregation; Parkinson’s disease; serine 129 phosphorylation; BiFC
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MDPI and ACS Style

Elsholz, L.; Wasser, Y.; Ziegler, P.; Habib, P.; Voigt, A. CK1BP Reduces α-Synuclein Oligomerization and Aggregation Independent of Serine 129 Phosphorylation. Cells 2021, 10, 2830. https://doi.org/10.3390/cells10112830

AMA Style

Elsholz L, Wasser Y, Ziegler P, Habib P, Voigt A. CK1BP Reduces α-Synuclein Oligomerization and Aggregation Independent of Serine 129 Phosphorylation. Cells. 2021; 10(11):2830. https://doi.org/10.3390/cells10112830

Chicago/Turabian Style

Elsholz, Lea, Yasmine Wasser, Patrick Ziegler, Pardes Habib, and Aaron Voigt. 2021. "CK1BP Reduces α-Synuclein Oligomerization and Aggregation Independent of Serine 129 Phosphorylation" Cells 10, no. 11: 2830. https://doi.org/10.3390/cells10112830

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