alpha-Synuclein has been implicated in the pathogenesis of Parkinson's disease. Although it is highly conserved, its physiological function has not yet been elucidated in detail. In an effort to define the function of alpha-synuclein, interacting proteins were screened in phage display assays. Prenylated Rab acceptor protein 1 (PRA1) was identified as an interacting partner. A selective interaction between alpha-synuclein and PRA1 was confirmed by coimmunoprecipitation and GST pull-down assays. PRA1 and alpha-synuclein were colocalized in N2a neuronal cells. Cotransfection of alpha-synuclein and PRA1 caused vesicles to accumulate in the periphery of the cytosol in neuronal cells, suggesting that overexpression of alpha-synuclein hinders proper vesicle trafficking and recycling as a result of the interaction between alpha-synuclein and PRA1. (C) 2011 Elsevier Inc. All rights reserved.