RNA editing of CAPS1 regulates synaptic vesicle organization, release and retrieval [article]

Randi J. Ulbricht, Sarah J. Sun, Claire E. DelBove, Kristina E. Kitko, Saad C. Rehman, Michelle Y. Wang, Roman M. Lazarenko, Qi Zhang, Ronald Emeson
2017 bioRxiv   pre-print
Calcium-dependent activator protein for secretion 1 (CAPS1) facilitates the docking and priming of synaptic and dense core vesicles. A conserved hairpin structure in the CAPS1 pre-mRNA allows an post-transcriptional adenosine-to-inosine RNA editing event to alter a genomically-encoded glutamate to a glycine codon. Functional comparisons of CAPS1 protein isoforms in primary hippocampal neurons show that elevation of edited CAPS1 isoforms facilitates presynaptic vesicle clustering and turnover.
more » ... ing and turnover. Conversely, non-edited CAPS1 isoforms slow evoked release, increase spontaneous fusion, and loosen the clustering of synaptic vesicles. Therefore, CAPS1 editing promotes organization of the vesicle pool in a way that is beneficial for evoked release, while non-edited isoforms promote more lax vesicle organization that widens distribution, attenuates evoked release and eases the control of spontaneous fusion. Overall, RNA editing of CAPS1 is a mechanism to fine tune neurotransmitter release.
doi:10.1101/178202 fatcat:bsvfcjgdbzfytl5vrmzndkqd3e