title: An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation.
abstract: Presynaptic assembly requires the packaging of requisite proteins into vesicular cargoes in the cell soma, their long-distance microtubule-dependent transport down the axon, and, finally, their reconstitution into functional complexes at prespecified sites. Despite the identification of several molecules that contribute to these events, the regulatory mechanisms defining such discrete states remain elusive. We report the characterization of an Arf-like small G protein, ARL-8, required during this process. arl-8 mutants prematurely accumulate presynaptic cargoes within the proximal axon of several neuronal classes, with a corresponding failure to assemble presynapses distally. This proximal accumulation requires the activity of several molecules known to catalyze presynaptic assembly. Dynamic imaging studies reveal that arl-8 mutant vesicles exhibit an increased tendency to form immotile aggregates during transport. Together, these results suggest that arl-8 promotes a trafficking identity for presynaptic cargoes, facilitating their efficient transport by repressing premature self-association.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Klassen
authors.forename: Ye E
authors.initials: YE
authors.lastname: Wu
authors.forename: Celine I
authors.initials: CI
authors.lastname: Maeder
authors.forename: Isei
authors.initials: I
authors.lastname: Nakae
authors.forename: Juan G
authors.initials: JG
authors.lastname: Cueva
authors.forename: Emily K
authors.initials: EK
authors.lastname: Lehrman
authors.forename: Minoru
authors.initials: M
authors.lastname: Tada
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.forename: George J
authors.initials: GJ
authors.lastname: Wang
authors.forename: Miriam
authors.initials: M
authors.lastname: Goodman
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Kenji
authors.initials: K
authors.lastname: Kontani
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
authors.forename: Kang
authors.initials: K
authors.lastname: Shen
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D050481:Vesicular Neurotransmitter Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes; D050481:Vesicular Neurotransmitter Transport Proteins; C097313:ADP-ribosylation factor related proteins; C477339:ARL5B protein, human; D020727:ADP-Ribosylation Factors