Axonal transport of synucleins is mediated by all rate components

Synculeins are abundant nerve terminal proteins of hitherto unknown functio n. In diseases with Lewy bodies, human alpha-synuclein concentrates in thes e lesions in the cell body and mutations in alpha-synculein lead to heritab le Parkinson's disease with Lewy bodies. This indicates that changes in the normal metabolism and axonal transport of alpha-synuclein is perturbed in these diseases. To investigate the normal axonal transport of synucleins we studied the rat visual system by nerve crush operations and metabolic labe lling of the retinal ganglion cells followed by immunoprecipitation of nerv e segments. We found by immunofluorescence microscopy of the crush-operated nerves that synculeins are transported by fast antero- and retrograde tran sport and colocalize with synaptophysin and SNAP-25 around the lesion. The metabolic labelling studies demonstrated that synucleins were moved through the nerve with all the rate components, the fast component and the slow co mponents a and b, with component b predominating. Two-dimensional gel elect rophoresis revealed that both alpha- and beta-synuclein migrate through the nerve by slow component b in a ratio of 2:1.