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PLK2 Modulates α-Synuclein Aggregation in Yeast and Mammalian Cells

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Abstract

Phosphorylation of α-synuclein (aSyn) on serine 129 is one of the major post-translation modifications found in Lewy bodies, the typical pathological hallmark of Parkinson’s disease. Here, we found that both PLK2 and PLK3 phosphorylate aSyn on serine 129 in yeast. However, only PLK2 increased aSyn cytotoxicity and the percentage of cells presenting cytoplasmic foci. Consistently, in mammalian cells, PLK2 induced aSyn phosphorylation on serine 129 and induced an increase in the size of the inclusions. Our study supports a role for PLK2 in the generation of aSyn inclusions by a mechanism that does not depend directly on serine 129 phosphorylation.

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Acknowledgments

This work was supported by Fundação para a Ciência e Tecnologia (PTDC/SAU-NEU/105215/2008 and PTDC/BIA-BCM/117975/2010) [SFRH/BPD/65890/2009 to Z.M., SFRH/BPD/35767/2007 to S.T., SFRH/BI/5177/2011 to P.A, SFRH/BD/79337/2011 to S.G]. TFO was supported by a Marie Curie International Reintegration Grant and an EMBO Installation Grant. EB is supported by EC Framework 7 Marie Curie Fellowship Training Network Grant (NEURASYNC) and by EU FP7 MEFOPA. SG was supported by AXA Research Fund.

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Authors and Affiliations

  1. Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisbon, Portugal

    Elisa Basso, Pedro Antas, Zrinka Marijanovic, Susana Gonçalves, Sandra Tenreiro & Tiago Fleming Outeiro

  2. Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    Tiago Fleming Outeiro

  3. Department of Neurodegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Göttingen, Germany

    Tiago Fleming Outeiro

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  1. Elisa Basso
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  2. Pedro Antas
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Correspondence to Tiago Fleming Outeiro.

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Elisa Basso and Pedro Antas have equal contribution.

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Fig. S1

PLK4 does not increase aSyn toxicity and foci formation. a Spotting assay of yeast cultures co-expressing aSyn (aSyn + EV) or empty vector (EV) with PLK4. The yeast cell suspensions were serial diluted (1/2) and applied as spots (4 μl) onto the surface of the solid medium either with glucose (control) or galactose (induced of aSyn and PLK4 expression) as carbon source. b Fluorescence microscopy and quantification of the number of cells presenting aSyn foci in cells expressing aSyn-GFP fusion protein alone (aSyn-GFP + EV) or together with PLK4. (JPEG 2223 kb)

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Basso, E., Antas, P., Marijanovic, Z. et al. PLK2 Modulates α-Synuclein Aggregation in Yeast and Mammalian Cells. Mol Neurobiol 48, 854–862 (2013). https://doi.org/10.1007/s12035-013-8473-z

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  • DOI: https://doi.org/10.1007/s12035-013-8473-z

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