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CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis.

Cell Rep. 2016 Nov 15;17(8):2004-2014
Kotaro Miyake 1 , Toshio Ohta 2 , Hisako Nakayama 3 , Nobutaka Doe 4 , Yuri Terao 5 , Eiji Oiki 5 , Izumi Nagatomo 6 , Yui Yamashita 7 , Takaya Abe 8 , Kazuko Nishikura 9 , Atsushi Kumanogoh 6 , Kouichi Hashimoto 3 , Yukio Kawahara 10
Kotaro Miyake 1 , Toshio Ohta 2 , Hisako Nakayama 3 , Nobutaka Doe 4 , Yuri Terao 5 , Eiji Oiki 5 , Izumi Nagatomo 6 , Yui Yamashita 7 , Takaya Abe 8 , Kazuko Nishikura 9 , Atsushi Kumanogoh 6 , Kouichi Hashimoto 3 , Yukio Kawahara 10
+ et al

[No authors listed]

Author information
  • 1 Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
  • 2 Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
  • 3 Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima 734-8551, Japan.
  • 4 General Education Center, Hyogo University of Health Sciences, Kobe, Hyogo 650-8530, Japan.
  • 5 Center for Medical Research and Education, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
  • 6 Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
  • 7 Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe, Hyogo 650-0047, Japan; Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Hyogo 650-0047, Japan.
  • 8 Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Hyogo 650-0047, Japan.
  • 9 The Wistar Institute, Philadelphia, PA 19104, USA.
  • 10 Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: ykawahara@rna.med.osaka-u.ac.jp.

摘要

Calcium-dependent activator protein for secretion 1 (CAPS1) plays a distinct role in the priming step of dense core vesicle (DCV) exocytosis. CAPS1 pre-mRNA 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.

KEYWORDS: ADAR, catecholamine, dense core vesicle, exocytosis, post-transcriptional modification, syntaxin-1A

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