This work demonstrates that α-synuclein inhibits the biosynthetic secretory pathway of mammalian cells potently and directly under nontoxic conditions and in the absence of insoluble α-synuclein aggregates. A potential mechanism involving α-synuclein binding to ER/Golgi SNAREs and inhibiting fusogenic SNARE complex assembly is elucidated.

As polarized cells, neurons maintain different sets of resident plasma membrane proteins in their axons and dendrites, which is consistent with the different roles that these neurites have in electrochemical signalling. Axonal and dendritic proteins are synthesized together within the somatodendritic domain; this raises a fundamental question: what is the nature of the intracellular trafficking machinery that ensures that these proteins reach the correct domain? Recent studies have advanced our understanding of the processes underlying the selective sorting and selective transport of axonal and dendritic proteins and have created potential avenues for future progress.

A novel assay based on expressing FRB-tagged candidate vesicle-binding protein reveals that KIF13A and KIF13B bind preferentially to early endosomes, whereas KIF1A and KIF1Bβ bind preferentially to late endosomes and lysosomes.