RNA Editing Mediates Oligomerization State of Calcium‐Dependent Activator Protein for Secretion 1 (CAPS1)

Abstract

CAPS1 RNA under‐goes a site‐specific adenosine‐to‐inosine RNA editing event that alters a genomically‐encod‐ed glutamate (GAG) to a glycine (GIG) codon within the encoded Calcium‐dependent activator protein for secretion 1 (CAPS1) protein. The protein isoforms generated from edited and non‐edited tran‐scripts have differential effects on synaptic vesicle distribution, release and recycling. Increasing expression of non‐edited CAPS1 isoforms negatively affects vesicle evoked release, leads to a more diffuse distribution of synaptic vesicles and increases spontaneous release from synaptic vesicles. Conversely, elevation of edited CAPS1 isoforms stimulates increased clustering of synaptic vesicles and decreased constitutive release from synaptic vesicles. We hypothesize that the mechanism for the distinct editing‐dependent phenotypes is related to the oligomerization state of CAPS1. To test this hypothesis, recombinant isoforms of edited and non‐edited CAPS1 were transfected into human embryonic kidney cells and detected by western blot of native PAGE. We find that non‐edited CAPS1 isoforms have a distinct oligomerization state from edited isoforms, suggesting that RNA editing influences the ability of CAPS1 to form larger complexes. Overall, we conclude that RNA editing serves as a molecular switch, allowing CAPS1 to self‐associate, thereby organizing vesicles into a tightly knit cluster that promotes robust, regu‐lat‐ed release and preventing release from vesicles in the absence of a stimulus.Support or Funding InformationThis work is supported by Missouri State University, Department of Biomedical Sciences.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.