The Association Between Alpha-Synuclein And Alpha-Tubulin In Brain Synapses

alpha-synuclein is a small protein that is mainly expressed in the synaptic terminals of nervous tissue. Although its implication in neurodegeneration is well established, the physiological role of alpha-synuclein remains elusive. Given its involvement in the modulation of synaptic transmission and the emerging role of microtubules at the synapse, the current study aimed at investigating whether alpha-synuclein becomes involved with this cytoskeletal component at the presynapse. We first analyzed the expression of alpha-synuclein and its colocalization with alpha-tubulin in murine brain. Differences were found between cortical and striatal/midbrain areas, with substantia nigra pars compacta and corpus striatum showing the lowest levels of colocalization. Using a proximity ligation assay, we revealed the direct interaction of alpha-synuclein with alpha-tubulin in murine and in human brain. Finally, the previously unexplored interaction of the two proteins in vivo at the synapse was disclosed in murine striatal presynaptic boutons through multiple approaches, from confocal spinning disk to electron microscopy. Collectively, our data strongly suggest that the association with tubulin/microtubules might actually be an important physiological function for alpha-synuclein in the synapse, thus suggesting its potential role in a neuropathological context.