a-Synuclein (a-syn) constitutes the major fibrillar component of Lewy bodies and Lewy neurites, and has been implicated in the pathogenesis of Parkinson’s disease (PD). Although a-syn is highly conserved, its normal function in the central nervous sys ...
a-Synuclein (a-syn) constitutes the major fibrillar component of Lewy bodies and Lewy neurites, and has been implicated in the pathogenesis of Parkinson’s disease (PD). Although a-syn is highly conserved, its normal function in the central nervous system remains unclear. a-syn has been known as a naively unstructured proteins, but it may acquire some secondary structures upon interaction with their partner(s).
In an effort to define functions from analysis of interacting partners, a phage display library, constructed using human brain cDNA library, has been employed to identify a-syn-interacting protein(s). Some phages that selectively bind to a-syn contained the prenylated Rab acceptor protein 1 (PRA1), vesicle t-SNARE interacting protein homologous 1B (VTI1B), and spectrin beta non-erythrocyte 1 (SPTBN1) cDNA fragments. Not only three candidate proteins were co-precipitated with a-syn in vitro, but also the overexpressed proteins in N2a mouse neuronal cells was co-immunoprecipitated with a-syn. PRA1, VTI1B, and SPTBN1 were also co-localized with a-syn. Co-transfection of a-syn with PRA1, VTI1B, and SPTBN1, showed effects on PRA1 movement to axon terminals, Subcellular distribution of vesicles, and neurite extension.
Our results suggest that a-syn, cooperated with PRA1, VTI1B, and SPTN1, may participate in vesicle trafficking, vesicle fusion with target membrane, and synaptic plasticity in neuronal cells, respectively.