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

Abstract | Full text | PDF | Supplemental material

Options: View larger image (or click on image)

Figure 2

Overexpression of Drosophila tyrosine kinase shark increases α-synuclein phosphorylation and ameliorates its neurotoxicity.

(A) Increased tyrosine phosphorylation in flies coexpressing shark and α-synuclein in the brain compared with flies expressing α-synuclein alone. Flies were 1 day old. (B–D) Quantitative analysis of TH-immunoreactive neurons in flies coexpressing shark and α-synuclein and flies expressing α-synuclein alone. Values represent mean ± SEM. Asterisks indicate that the difference in TH-immunoreactive dopaminergic neuronal number between the 2 genotypes at the time points examined is statistically significant (*P < 0.01, **P < 0.05, multivariant ANOVA with supplementary Newman-Keuls test). The driver in A–D was elav-GAL4. (E–G) Augmented tyrosine phosphorylation suppresses retinal toxicity. Retinal degeneration in flies expressing α-syn^S129D (E) is largely prevented by coexpressing shark (F). Original magnification in E and F, ×400. (G) Quantitative comparison demonstrating significant rescue of the percentage of normal photoreceptor clusters in α-syn^S129D transgenic flies expressing shark (*P < 0.01, Student’s t test). Error bars represent SEM. The driver in E–G was GMR-GAL4. Flies were 30 days old.