Molecular interaction of α-synuclein with tubulin influences on the polymerization of microtubule in vitro and structure of microtubule in cells

Microtubule dynamics is essential for many vital cellular processes such as in intracellular transport, metabolism, and cell division. Evidences demonstrate that alpha-synuclein may associate with microtubular cytoskeleton and its major component, tubulin. In the present study, the molecular interaction between alpha-synuclein and tubulin was confirmed by GST pull-down assay and co-immunoprecipitation. The interacting regions within alpha-synuclein with tubulin were mapped at the residues 60-100 of alpha-synuclein that is critical for the binding activity with tubulin. Microtubule assembly assays and sedimentation tests demonstrated that alpha-synuclein influenced the polymerization of tubulin in vitro, revealing an interacting region-dependent feature. Confocal microscopy detected that exposures of alpha-synuclein proteins inhibited microtubule formation in the cultured cells, with a length-dependent phenomenon. Our data highlight a potential role of alpha-synuclein in regulating the microtubule dynamics in neurons. The association of alpha-synuclein with tubulin may further provide insight into the biological and pathophysiological function of synuclein.