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

Neuron. 2010 Jun 10;66(5):710-23. doi: 10.1016/j.neuron.2010.04.033.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / physiology*
  • Animals
  • Axonal Transport / genetics
  • Axonal Transport / physiology*
  • Caenorhabditis elegans
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Multiprotein Complexes / antagonists & inhibitors
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Protein Transport / genetics
  • Synaptic Vesicles / genetics
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Vesicular Neurotransmitter Transport Proteins / antagonists & inhibitors*
  • Vesicular Neurotransmitter Transport Proteins / genetics
  • Vesicular Neurotransmitter Transport Proteins / metabolism

Substances

  • Membrane Proteins
  • Multiprotein Complexes
  • Vesicular Neurotransmitter Transport Proteins
  • ADP-ribosylation factor related proteins
  • ARL5B protein, human
  • ADP-Ribosylation Factors