title: The slow axonal transport of alpha-synuclein--mechanistic commonalities amongst diverse cytosolic cargoes.
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 overall-solubility 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.
authors.affiliation: Department of Pathology, University of California, San Diego, California 92093, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Utpal
authors.initials: U
authors.lastname: Das
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.forename: Subhojit
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D051379:Mice; D016704:Synapsins / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D016704:Synapsins; D051844:alpha-Synuclein