BORC Regulates the Axonal Transport of Synaptic Vesicle Precursors by Activating ARL-8

Shinsuke Niwa, Li Tao, Sharon Y. Lu, Gerald M. Liew, Wei Feng, Maxence V. Nachury, Kang Shen

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Axonal transport of synaptic vesicle precursors (SVPs) is essential for synapse development and function. The conserved ARF-like small GTPase ARL-8 is localized to SVPs and directly activates UNC-104/KIF1A, the axonal-transport kinesin for SVPs in C. elegans. It is not clear how ARL-8 is activated in this process. Here we show that part of the BLOC-1-related complex (BORC), previously shown to regulate lysosomal transport, is required to recruit and activate ARL-8 on SVPs. We found mutations in six BORC subunits—blos-1/BLOS1, blos-2/BLOS2, snpn-1/Snapin, sam-4/Myrlysin, blos-7/Lyspersin, and blos-9/MEF2BNB—cause defects in axonal transport of SVPs, leading to ectopic accumulation of synaptic vesicles in the proximal axon. This phenotype is suppressed by constitutively active arl-8 or unc-104 mutants. Furthermore, SAM-4/Myrlysin, a subunit of BORC, promotes the GDP-to-GTP exchange of ARL-8 in vitro and recruits ARL-8 onto SVPs in vivo. Thus, BORC regulates the axonal transport of synaptic materials and synapse formation by controlling the nucleotide state of ARL-8. Interestingly, the other two subunits of BORC essential for lysosomal transport, kxd-1/KXD1 and blos-8/Diaskedin, are not required for the SVP transport, suggesting distinct subunit requirements for lysosomal and SVP trafficking.

Original languageEnglish
Pages (from-to)2569-2578.e4
JournalCurrent Biology
Volume27
Issue number17
DOIs
Publication statusPublished - 2017 Sep 11

Keywords

  • ARL-8
  • BORC
  • KIF1A
  • UNC-104
  • axonal transport
  • synapse
  • synaptic vesicles

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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