@article{b892de7b892a4f8a8effce40dd147165,
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.",
keywords = "Cellbio, Molneuro, Signaling",
author = "Klassen, {Matthew P.} and Wu, {Ye E.} and Maeder, {Celine I.} and Isei Nakae and Cueva, {Juan G.} and Lehrman, {Emily K.} and Minoru Tada and Keiko Gengyo-Ando and Wang, {George J.} and Miriam Goodman and Shohei Mitani and Kenji Kontani and Toshiaki Katada and Kang Shen",
note = "Funding Information: This work was supported by the Howard Hughes Medical Institute, the Human Frontier Science Foundation, and the W.M. Keck Foundation. We thank the International C. elegans Gene Knockout Consortium, the National Bioresource Project (Japan), and the laboratories of C. Bargmann, G. Lesa, and Y. Jin for strains; D. Klopfenstein and S. Munro for reagents; and I. Kolotuev, Y. Schwab, and M. Labouesse for assistance with correlative EM. We also thank C. Gao and Y. Fu for technical assistance and S. Sigrist and S. Munro for thoughtful comments on the manuscript. M.P.K. identified the mutation for arl-8(wy271). Y.E.W. and M.P.K. characterized the mutant phenotype and performed the genetic interaction experiments. C.I.M. performed the dynamic imaging experiments. E.K.L. isolated the wy271 mutation. I.N., M.T., T.K., and K.K. performed the aldicarb assays and western blot analysis. J.G.C., G.J.W., and M.G. performed the EM analysis. K.G.-A. and S.M. generated the arl-8(tm2504) and arl-8(tm2388) alleles. K.S. supervised the project. M.P.K., Y.E.W., and K.S. wrote the paper. ",
year = "2010",
month = jun,
doi = "10.1016/j.neuron.2010.04.033",
language = "English",
volume = "66",
pages = "710--723",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}