alpha-Synuclein is the major component of Lewy bodies and Lewy neurites, the pathological hallmarks of surviving neuronal cells in Parkinson's disease patients. However, the physiological role played by alpha-synuclein remains unclear. In this study, spectrin beta non-erythrocyte 1 (SPTBN1) interacted with a-synuclein in phage display assays using a normalized human brain cDNA library. A direct interaction between alpha-synuclein and SPTBN1 was confirmed by GST pull-down and co-immunoprecipitation assays. SPTBN1 and alpha-synuclein proteins colocalized in N2a neuronal cells. Transfection of SPTBN1 caused human SHSY5Y dopaminergic neuron cells to inappropriately induce neurites, which extended from cell bodies. Cotransfection with alpha-synuclein reversed SPTBN1-induced excessive neurite branching in SH-SY5Y cells, and only a single neurite extended from each neuron. These results suggest that a-synuclein modulates neurite outgrowth by interacting with cytoskeletal proteins such as SPTBN1. (C) 2012 Elsevier Inc. All rights reserved.