title: The balance between capture and dissociation of presynaptic proteins controls the spatial distribution of synapses.
abstract: The location, size, and number of synapses critically influence the specificity and strength of neural connections. In axons, synaptic vesicle (SV) and active zone (AZ) proteins are transported by molecular motors and accumulate at discrete presynaptic loci. Little is known about the mechanisms coordinating presynaptic protein transport and deposition to achieve proper distribution of synaptic material. Here we show that SV and AZ proteins exhibit extensive cotransport and undergo frequent pauses. At the axonal and synaptic pause sites, the balance between the capture and dissociation of mobile transport packets determines the extent of presynaptic assembly. The small G protein ARL-8 inhibits assembly by promoting dissociation, while a JNK kinase pathway and AZ assembly proteins inhibit dissociation. Furthermore, ARL-8 directly binds to the UNC-104/KIF1A motor to limit the capture efficiency. Together, molecular regulation of the dichotomy between axonal trafficking and local assembly controls vital aspects of synapse formation and maintenance.
authors.affiliation: Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ye E
authors.initials: YE
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Huo
authors.forename: Celine I
authors.initials: CI
authors.lastname: Maeder
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Kang
authors.initials: K
authors.lastname: Shen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D020558:GTP Phosphohydrolases; C552949:arl-8 protein, C elegans