The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport

Axonal transport of synaptic vesicles (svs) is a kif1a/unc-104 mediated process critical for synapse development and maintenance yet little is known of how sv transport is regulated. using c. elegans as an in vivo model,we identified sam-4 as a novel conserved vesicular component regulating sv transport. processivity,but not velocity,of sv transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. gain-of-function mutations in the unc-104 motor domain,identified in this study,suppress the sam-4 defects by increasing processivity of the sv transport. genetic analyses suggest that sam-4,syd-2/liprin-α and the kif1a/unc-104 motor function in the same pathway to regulate sv transport. our data support a model in which the sv protein sam-4 regulates the processivity of sv transport. © 2014 zheng et al.