Abstract
Synaptic vesicles (SV) store various neurotransmitters that are released at the synapse. The molecular mechanisms of biogenesis, exocytosis, and endocytosis for SV, however, remain largely elusive. In this study, using Complex Object Parametric Analysis and Sorter (COPAS) to monitor the fluorescence of synapto-pHluorin (SpH), we performed a whole-genome RNAi screen in C. elegans to identify novel genetic modulators in SV cycling. One hundred seventy six genes that up-regulating SpH fluorescence and 96 genes that down-regulating SpH fluorescence were identified after multi-round screen. Among these genes, B0035.1 (bugz-1) encodes ortholog of mammalian C2H2 zinc-finger protein BuGZ/ZNF207, which is a spindle assembly checkpoint protein essential for mitosis in human cells. Combining electrophysiology, imaging and behavioral assays, we reveal that depletion of BuGZ-1 results in defects in locomotion. We further demonstrate that BuGZ-1 promotes SV recycling by regulating the expression levels of endocytosis-related genes such as rab11.1. Therefore, we have identified a bunch of potential genetic modulators in SV cycling, and revealed an unexpected role of BuGZ-1 in regulating synaptic transmission.
Highlights
Synaptic vesicles (SV) store neurotransmitters, concentrate in the presynaptic nerve terminals, and undergo Ca2+-dependent exocytosis
In order to get a clearer picture of the SV cycling, we aimed to identify novel genes required for synaptic vesicle cycling via C. elegans whole-genome RNAi screen, using SpH as the probe
To identify novel genes related to synaptic vesicle (SV) cycling, we performed an automatic whole-genome RNAi screen in C. elegans
Summary
Synaptic vesicles (SV) store neurotransmitters, concentrate in the presynaptic nerve terminals, and undergo Ca2+-dependent exocytosis These steps include biogenesis of SVs, transport to release sites, docking with plasma membrane, priming, and calcium-triggered fusion (Sudhof and Rizo, 2011; Rizo and Xu, 2015). All three SNARE proteins that catalyze exocytosis—synaptobrevin, SNAP25, and syntaxin are needed for endocytosis initiation (Sudhof and Rizo, 2011; Wu et al, 2014; Xie et al, 2017) Some molecules such as amphiphysin, endophilin, AP180, auxilin, and dynamin have been implicated to be involved in endocytosis (Wu et al, 2014). The principle steps and some molecules have been identified, the exact mechanisms of biogenesis, exocytosis and endocytosis of SVs remain largely elusive
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
