α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

Michela Zaltieri, Jessica Grigoletto, Francesca Longhena, Laura Navarria, Gaia Favero, Stefania Castrezzati, Maria Alessandra Colivicchi, Laura Della Corte, Rita Rezzani, Marina Pizzi, Fabio Benfenati, Maria Grazia Spillantini, Cristina Missale, PierFranco Spano, Arianna Bellucci

Research output: Contribution to journalArticle

Abstract

The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain α-synuclein (α-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that α-syn interacts with and modulates synapsin III. The absence of α-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In α-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in α-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of α-syn and synapsin III in the regulation of dopamine neuron synaptic function.

Original languageEnglish
Pages (from-to)2231-2243
Number of pages13
JournalJournal of Cell Science
Volume128
Issue number13
DOIs
Publication statusPublished - 2015

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Keywords

  • Dopamine release
  • Parkinson's disease
  • Synapsin III
  • Synaptic vesicles
  • α-synuclein

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zaltieri, M., Grigoletto, J., Longhena, F., Navarria, L., Favero, G., Castrezzati, S., Colivicchi, M. A., Corte, L. D., Rezzani, R., Pizzi, M., Benfenati, F., Spillantini, M. G., Missale, C., Spano, P., & Bellucci, A. (2015). α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons. Journal of Cell Science, 128(13), 2231-2243. https://doi.org/10.1242/jcs.157867