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

被引:87
|
作者
Zaltieri, Michela [1 ]
Grigoletto, Jessica [1 ]
Longhena, Francesca [1 ]
Navarria, Laura [1 ]
Favero, Gaia [2 ]
Castrezzati, Stefania [2 ]
Colivicchi, Maria Alessandra [3 ]
Della Corte, Laura [3 ]
Rezzani, Rita [2 ]
Pizzi, Marina [1 ,6 ]
Benfenati, Fabio [4 ]
Spillantini, Maria Grazia [5 ]
Missale, Cristina [1 ]
Spano, PierFranco [1 ,6 ]
Bellucci, Arianna [1 ]
机构
[1] Univ Brescia, Dept Mol & Translat Med, I-25123 Brescia, Italy
[2] Univ Brescia, Dept Clin & Expt Sci, I-25123 Brescia, Italy
[3] Univ Florence, NEUROFARBA Dept, I-50139 Florence, Italy
[4] Italian Inst Technol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy
[5] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0QH, England
[6] IRCCS San Camillo Hosp NHS Italy, Neurorehabil Unit, I-30126 Venice Lido, Italy
关键词
alpha-synuclein; Dopamine release; Parkinson's disease; Synapsin III; Synaptic vesicles; LEWY BODY DISEASE; PARKINSONS-DISEASE; NEUROTRANSMITTER RELEASE; SUBSTANTIA-NIGRA; MOUSE MODEL; MICE; OVEREXPRESSION; REDISTRIBUTION; AGGREGATION; PLASTICITY;
D O I
10.1242/jcs.157867
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 alpha-synuclein (alpha-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 alpha-syn interacts with and modulates synapsin III. The absence of alpha-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In alpha-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 alpha-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 alpha-syn and synapsin III in the regulation of dopamine neuron synaptic function.
引用
收藏
页码:2231 / 2243
页数:13
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