bioRxiv Biochemistry
bioRxiv Biochemistry
5 years ago

RNA editing of CAPS1 regulates synaptic vesicle organization, release and retrieval.

Kitko, S. C., K. E., R., Emeson, Rehman, Q., Lazarenko, DelBove, Ulbricht, C. E., Sun, M. Y., Wang, R. M., Zhang, S. J., R. J.
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. 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.

Publisher URL: http://biorxiv.org/cgi/content/short/178202v1

DOI: 10.1101/178202

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