The slow axonal transport of alpha-synuclein--mechanistic commonalities amongst diverse cytosolic cargoes.

Cytoskeleton
Yong TangSubhojit Roy

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.

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Citations

Sep 27, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yong TangSubhojit Roy
Jul 25, 2015·Computer Methods in Biomechanics and Biomedical Engineering·I A Kuznetsov, A V Kuznetsov
Apr 17, 2013·Brain Pathology·Sonia GeorgePatrik Brundin
Oct 31, 2012·Annals of Neurology·Eric C FreundtMichel Brahic
Aug 6, 2013·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Subhojit Roy
Jun 1, 2017·The Journal of Cell Biology·Archan GangulySubhojit Roy
Dec 5, 2020·Scientific Reports·Eleonora PeregoSarah Köster
Mar 12, 2021·Current Opinion in Cell Biology·Sofiia Reshetniak, Silvio O Rizzoli
Jun 3, 2021·International Journal of Molecular Sciences·Panagiota Mavroeidi, Maria Xilouri
Dec 11, 2021·Mathematical Biosciences·Ivan A Kuznetsov, Andrey V Kuznetsov

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