Redistribution of DAT/α-synuclein complexes visualized by "in situ" proximity ligation assay in transgenic mice modelling early Parkinson's disease

Arianna Bellucci, Laura Navarria, Elisa Falarti, Michela Zaltieri, Federica Bono, Ginetta Collo, Maria Grazia, Cristina Missale, PierFranco Spano

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Abstract

Alpha-synuclein, the major component of Lewy bodies, is thought to play a central role in the onset of synaptic dysfunctions in Parkinson's disease (PD). In particular, α-synuclein may affect dopaminergic neuron function as it interacts with a key protein modulating dopamine (DA) content at the synapse: the DA transporter (DAT). Indeed, recent evidence from our "in vitro" studies showed that α-synuclein aggregation decreases the expression and membrane trafficking of the DAT as the DAT is retained into α-synuclein-immunopositive inclusions. This notwithstanding, "in vivo" studies on PD animal models investigating whether DAT distribution is altered by the pathological overexpression and aggregation of α-synuclein are missing. By using the proximity ligation assay, a technique which allows the "in situ" visualization of protein-protein interactions, we studied the occurrence of alterations in the distribution of DAT/α-synuclein complexes in the SYN120 transgenic mouse model, showing insoluble α-synuclein aggregates into dopaminergic neurons of the nigrostriatal system, reduced striatal DA levels and an altered distribution of synaptic proteins in the striatum. We found that DAT/α-synuclein complexes were markedly redistributed in the striatum and substantia nigra of SYN120 mice. These alterations were accompanied by a significant increase of DAT striatal levels in transgenic animals when compared to wild type littermates. Our data indicate that, in the early pathogenesis of PD, α-synuclein acts as a fine modulator of the dopaminergic synapse by regulating the subcellular distribution of key proteins such as the DAT.

Original languageEnglish
Article numbere27959
JournalPLoS One
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 7 2011

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bellucci, A., Navarria, L., Falarti, E., Zaltieri, M., Bono, F., Collo, G., Grazia, M., Missale, C., & Spano, P. (2011). Redistribution of DAT/α-synuclein complexes visualized by "in situ" proximity ligation assay in transgenic mice modelling early Parkinson's disease. PLoS One, 6(12), [e27959]. https://doi.org/10.1371/journal.pone.0027959