title: CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima 734-8551, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: General Education Center, Hyogo University of Health Sciences, Kobe, Hyogo 650-8530, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Doe
authors.affiliation: Center for Medical Research and Education, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Terao
authors.affiliation: Center for Medical Research and Education, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oiki
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagatomo
authors.affiliation: 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.
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Hyogo 650-0047, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishikura
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.affiliation: Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima 734-8551, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: 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.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kawahara
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D055162:Biocatalysis; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D004734:Energy Metabolism; D005089:Exocytosis; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D016716:PC12 Cells; D010805:Physical Conditioning, Animal; D011485:Protein Binding; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D002395:Catecholamines; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D050827:Syntaxin 1; C000599465:ADAR1 protein, mouse; C000595151:ADAR2 protein, mouse; D000243:Adenosine Deaminase
keywords: ADAR; catecholamine; dense core vesicle; exocytosis; post-transcriptional modification; syntaxin-1A