The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport

• Published in: PLoS genetics Vol. 10; no. 10; p. e1004644
• Main Authors: Zheng, Qun, Ahlawat, Shikha, Schaefer, Anneliese, Mahoney, Tim, Koushika, Sandhya P, Nonet, Michael L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2014; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Genetically Modified; Axonal transport; Axonal Transport - genetics; Binding Sites; Biology and Life Sciences; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Genetic aspects; Genetic regulation; Genetic research; Intercellular Signaling Peptides and Proteins; Medicine and Health Sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Nematodes; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurites - metabolism; Neurons; Neurons - metabolism; Paralysis; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation; Proteins; Research and Analysis Methods; Synapses; Synaptic Vesicles - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004644

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.