TY - JOUR
T1 - α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons
AU - Zaltieri, Michela
AU - Grigoletto, Jessica
AU - Longhena, Francesca
AU - Navarria, Laura
AU - Favero, Gaia
AU - Castrezzati, Stefania
AU - Colivicchi, Maria Alessandra
AU - Corte, Laura Della
AU - Rezzani, Rita
AU - Pizzi, Marina
AU - Benfenati, Fabio
AU - Spillantini, Maria Grazia
AU - Missale, Cristina
AU - Spano, PierFranco
AU - Bellucci, Arianna
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Dopamine release
KW - Parkinson's disease
KW - Synapsin III
KW - Synaptic vesicles
KW - α-synuclein
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UR - http://www.scopus.com/inward/citedby.url?scp=84935491802&partnerID=8YFLogxK
U2 - 10.1242/jcs.157867
DO - 10.1242/jcs.157867
M3 - Article
C2 - 25967550
AN - SCOPUS:84935491802
VL - 128
SP - 2231
EP - 2243
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 13
ER -