An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation.
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.
Klassen
Matthew P
MP
Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA 94305, USA.
Wu
Ye E
YE
Maeder
Celine I
CI
Nakae
Isei
I
Cueva
Juan G
JG
Lehrman
Emily K
EK
Tada
Minoru
M
Gengyo-Ando
Keiko
K
Wang
George J
GJ
Goodman
Miriam
M
Mitani
Shohei
S
Kontani
Kenji
K
Katada
Toshiaki
T
Shen
Kang
K
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
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