An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation.

An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation.
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DOI:
10.1016/j.neuron.2010.04.033
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发表时间:
2010-06-10
期刊:
影响因子:
16.2
通讯作者:
Shen, Kang
Shen, Kang
中科院分区:
医学1区
文献类型:
--
作者:
Klassen, Matthew P.;Wu, Ye E.;Maeder, Celine I.;Nakae, Isei;Cueva, Juan G.;Lehrman, Emily K.;Tada, Minoru;Gengyo-Ando, Keiko;Wang, George J.;Goodman, Miriam;Mitani, Shohei;Kontani, Kenji;Katada, Toshiaki;Shen, Kang

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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.
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