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Keywords:

  • cytosolic synaptic proteins;
  • synapsin;
  • α-synuclein;
  • slow axonal transport;
  • transport packets;
  • cargo complexes;
  • diffusion;
  • slow component-b, SCb

Abstract

Slow axonal transport conveys perikaryally-synthesized cytosolic proteins in a rate-class called Slow Component-b (SCb). One such protein—α-synuclein—is largely conveyed in SCb, and is also a key player in a group of neurodegenerative diseases called synucleinopathies. Axonal transport defects of α-synuclein have been hypothesized to play a role in synucleinopathies, but mechanisms moving α-synuclein in slow axonal transport are unclear. Here we use a recently developed model-system in our laboratory to visualize the slow transport of α-synuclein, comparing it to another SCb protein synapsin. Despite differences inbiological properties and overallsolubility in axons, the anterograde transport of both SCb proteins was strikingly similar, suggesting commonalities in slow axonal transport mechanisms of seemingly diverse cytosolic cargoes. The data support a model where SCb proteins dynamically organize into ‘transport-competent’ complexes that are conveyed via transient associations with other persistently-moving cargoes (“mobile-units”). The identity of the latter is yet unknown. Visualizing normal α-synuclein transport may also open the door to studies of α-synuclein transport in pathologic states. © 2012 Wiley Periodicals, Inc.