JCI - Tyrosine and serine phosphorylation of α-synuclein have opposing effects on neurotoxicity and soluble oligomer formation

Tyrosine and serine phosphorylation of α-synuclein have opposing effects on neurotoxicity and soluble oligomer formation

Li Chen, Magali Periquet, Xu Wang, Alessandro Negro, Pamela J. McLean, Bradley T. Hyman, Mel B. Feany

Published in Volume 119, Issue 11

J Clin Invest. 2009; 119(11):3257–3265 doi:10.1172/JCI39088

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Figure 3

α-Synuclein toxicity correlates with accumulation of soluble high-molecular-weight oligomers.

(A) Representative immunoblot of soluble fractions from brain homogenates run on a 4%–12% gradient gel shows increased oligomer formation in flies expressing α-syn^S129D and decreased oligomer formation in flies expressing α-syn^S129A. Aliquots of the same protein preparations were loaded on a separate 10%–20% gel to visualize monomeric α-synuclein and tubulin. Control genotype: elav-GAL4. (B) Quantitative analysis of oligomer formation using densitometry. Values represent mean ± SEM of 3 independent experiments. Single asterisk indicates the significantly increased accumulation of high-molecular-weight species in flies expressing α-syn^S129D (*P < 0.01, multivariant ANOVA with supplementary Newman-Keuls test) at 10 days. Double asterisks indicate the significantly decreased accumulation in α-syn^S129A flies at 20 days (**P < 0.01, multivariant ANOVA with supplementary Newman-Keuls test). (C) Coexpression of the serine kinase Gprk2 with α-syn^WT increases high-molecular-weight α-synuclein species. Flies were 10 days old.