Journal
CELL REPORTS
Volume 17, Issue 8, Pages 2004-2014Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.10.073
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [21112515, 15H01471, 26292150]
- Takeda Medical Research Foundation
- Suzuken Memorial Foundation
- US National Institutes of Health [R01 GM040536, R01 CA17508]
- Ellison Medical Foundation [AG-SS-228-09]
- Macula Vision Research Foundation
- Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health
- Grants-in-Aid for Scientific Research [21112515, 26292150, 16K07100, 15H01471] Funding Source: KAKEN
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Calcium-dependent activator protein for secretion 1 (CAPS1) plays a distinct role in the priming step of dense core vesicle (DCV) exocytosis. CAPS1 premRNA is known to undergo adenosine-to-inosine RNA editing in its coding region, which results in a glutamate-to-glycine conversion at a site in its C-terminal region. However, the physiological significance of CAPS1 RNA editing remains elusive. Here, we created mutant mice in which edited CAPS1 was solely expressed. These mice were lean due to increased energy expenditure caused by physical hyperactivity. Electrophysiological and biochemical analyses demonstrated that the exocytosis of DCVs was upregulated in the chromaffin cells and neurons of these mice. Furthermore, we showed that edited CAPS1 bound preferentially to the activated form of syntaxin-1A, a component of the exocytotic fusion complex. These findings suggest that RNA editing regulates DCV exocytosis in vivo, affecting physical activity.
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