RETRACTED ARTICLE: Differential regulation of wild-type and mutant alpha-synuclein binding to synaptic membranes by cytosolic factors
Authors: Weimin Hou
Anurag Tandon
Diana Marsilio
Sabine Wislet-Gendebien
Shawn N Whitehead
Naomi P Visanji
Paul E Fraser
Steffany A L Bennett
Daniel Figeys
Journal: BMC Neuroscience (2008)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Alpha-Synuclein; Parkinson's disease; Membrane binding; Cytosolic factors; Mutations
Affiliations: Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, M5S 3H2 Canada. 

Abstract:  Background: Alpha-Synuclein (alpha-syn), a 140 amino acid protein associated with presynaptic membranes in brain, is a major constituent of Lewy bodies in Parkinson's disease (PD). Three missense mutations (A30P, A53T and E46K) in the alpha-syn gene are associated with rare autosomal dominant forms of familial PD. However, the regulation of alpha-syn's cellular localization in neurons and the effects of the PD-linked mutations are poorly understood. Results: In the present study, we analysed the ability of cytosolic factors to regulate alpha-syn binding to synaptic membranes. We show that co-incubation with brain cytosol significantly increases the membrane binding of normal and PD-linked mutant alpha-syn. To characterize cytosolic factor(s) that modulate alpha-syn binding properties, we investigated the ability of proteins, lipids, ATP and calcium to modulate alpha-syn membrane interactions. We report that lipids and ATP are two of the principal cytosolic components that modulate Wt and A53T alpha-syn binding to the synaptic membrane. We further show that 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0 PAF) is one of the principal lipids found in complex with cytosolic proteins and is required to enhance alpha-syn interaction with synaptic membrane. In addition, the impaired membrane binding observed for A30P alpha-syn was significantly mitigated by the presence of protease-sensitive factors in brain cytosol. Conclusion: These findings suggest that endogenous brain cytosolic factors regulate Wt and mutant alpha-syn membrane binding, and could represent potential targets to influence alpha-syn solubility in brain. 

Retracted: Yes

PubPeer comments:
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 Figure 5D. * Marked in green: the Synaptophysin panels appear to look very similar. * Marked in orange: the a-synuclein panels appear to look very similar if one of the two is shifted one lane, and stretched vertically. ![file] , 
 Retraction Note Published: 03 June 2021  The Editor has retracted this article. Concerns have been raised with a number of figures, specifically: Figure 1C: The right three blots of the upper left hand band appear to be identical to the right three blots of the upper right hand band. Figure 5D: the Synaptophysin panels for both 1 minute-cross linking and 3 minute cross-linking appear to be identical. Figure 5D: the a-synuclein panels appear to look very similar. The Editor therefore no longer has confidence in the reliability of the data reported in the article. Sabine Wislet-Gendebien does not agree to this retraction. Naomi P Visanji, Shawn N Whitehead, Diana Marsilio, Weimin Hou, Daniel Figeys, Paul E Fraser, Steffany AL Bennett and Anurag Tandon agree to this retraction. ,