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.