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

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

doi:10.1101/178202

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bioRxiv · 10.1101/178202

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

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

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Abstract

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.\n\nIMPACT STATEMENTPost-transcriptional RNA editing of CAPS1 is a mechanism to regulate neurotransmitter release from synaptic vesicles.

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Ulbricht, R. J., Sun, S. J., DelBove, C. E., Kitko, K. E., Rehman, S. C., Wang, M. Y., Lazarenko, R. M., Zhang, Q., Emeson, R.. 2017-08-18. RNA editing of CAPS1 regulates synaptic vesicle organization, release and retrieval.. https://doi.org/10.1101/178202

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