Sumoylated α-synuclein translocates into the nucleus by karyopherin α6

Abstract

α-Synuclein (α-SYN) is uniquely found in the brains of Parkinson’s disease (PD) patients and it has been the major target of PD research for many years. The translocation of α-SYN into the nucleus of neuronal cells is a well-known fact but the mode of nuclear entry and its functions thereafter are not well defined. By utilizing a model cell line and primary cultured neurons, we have investigated a plausible mechanism of α-SYN nuclear translocation and its pathophysiological roles in the nucleus of cells with neuronal phenotypes. We, first, identified that cytosolic α-SYN proteins bind to karyopherin alpha6 proteins only after sumoylation (i.e. SUMO2/3 binding) and then transits through the nuclear pore complex (NPC) as a complexed entity. We investigated that the nuclear translocation of α-SYN is critically required for its nuclear translocation and that this process is mediated by karyopherin alpha6.