Quantitative Analysis of α-Synuclein Solubility in Living Cells Using Split GFP Complementation

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dc.citation.firstpagee43505
dc.citation.issueNumber8
dc.citation.journalTitlePLoS ONE
dc.citation.volumeNumber7
dc.contributor.authorKothawala, Ahmed
dc.contributor.authorKilpatrick, Kiri
dc.contributor.authorNovoa, Jose Andres
dc.contributor.authorSegatori, Laura
dc.date.accessioned2015-01-06T19:20:34Z
dc.date.available2015-01-06T19:20:34Z
dc.date.issued2012
dc.description.abstractPresently incurable, Parkinson's disease (PD) is the most common neurodegenerative movement disorder and affects 1% of the population over 60 years of age. The hallmarks of PD pathogenesis are the loss of dopaminergic neurons in the substantia nigra pars compacta, and the occurrence of proteinaceous cytoplasmic inclusions (Lewy bodies) in surviving neurons. Lewy bodies are mainly composed of the pre-synaptic protein alpha-synuclein (αsyn), an intrinsically unstructured, misfolding-prone protein with high propensity to aggregate. Quantifying the pool of soluble αsyn and monitoring αsyn aggregation in living cells is fundamental to study the molecular mechanisms of αsyn-induced cytotoxicity and develop therapeutic strategies to prevent αsyn aggregation. In this study, we report the use of a split GFP complementation assay to quantify αsyn solubility. Particularly, we investigated a series of naturally occurring and rationally designed αsyn variants and showed that this method can be used to study how αsyn sequence specificity affects its solubility. Furthermore, we demonstrated the utility of this assay to explore the influence of the cellular folding network on αsyn solubility. The results presented underscore the utility of the split GFP assay to quantify αsyn solubility in living cells.
dc.identifier.citationKothawala, Ahmed, Kilpatrick, Kiri, Novoa, Jose Andres, et al.. "Quantitative Analysis of α-Synuclein Solubility in Living Cells Using Split GFP Complementation." <i>PLoS ONE,</i> 7, no. 8 (2012) Public Library of Science: e43505. http://dx.doi.org/10.1371/journal.pone.0043505.
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0043505
dc.identifier.urihttps://hdl.handle.net/1911/78897
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleQuantitative Analysis of α-Synuclein Solubility in Living Cells Using Split GFP Complementation
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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