Subcellular localisation of recombinant α- and γ-synuclein

α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein-eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. However, γ-synuclein lacks a C-terminal domain that causes nuclear localisation of the fusion protein, suggesting that the two synucleins might have different roles relating to the cell nucleus.