RRC ID 49258
著者 Niwa S, Tao L, Lu SY, Liew GM, Feng W, Nachury MV, Shen K.
タイトル BORC Regulates the Axonal Transport of Synaptic Vesicle Precursors by Activating ARL-8.
ジャーナル Curr Biol
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.
巻・号 27(17)
ページ 2569-2578.e4
公開日 2017-9-11
DOI 10.1016/j.cub.2017.07.013
PII S0960-9822(17)30871-0
PMID 28823680
PMC PMC5693321
MeSH Animals Axonal Transport / genetics* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Synaptic Vesicles / physiology*
IF 9.601
引用数 20
リソース情報
線虫 tm1159 tm1892 tm2388 tm3828 tm6384