title: The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri, United States of America.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Ahlawat
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri, United States of America; Department of Neurology, Washington University Medical School, St. Louis, Missouri, United States of America.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Schaefer
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri, United States of America; Huffington Center On Aging, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Mahoney
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India.
authors.forename: Sandhya P
authors.initials: SP
authors.lastname: Koushika
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nonet
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001370:Axonal Transport / Q000235:genetics; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C000607058:SAM-4 protein, C elegans; C490598:SYD-2 protein, C elegans; C423186:UNC-104 protein, C elegans