TY - JOUR
T1 - Opposing roles for SNAP23 in secretion in exocrine and endocrine pancreatic cells
AU - Kunii, Masataka
AU - Ohara-Imaizumi, Mica
AU - Takahashi, Noriko
AU - Kobayashi, Masaki
AU - Kawakami, Ryosuke
AU - Kondoh, Yasumitsu
AU - Shimizu, Takeshi
AU - Simizu, Siro
AU - Lin, Bangzhong
AU - Nunomura, Kazuto
AU - Aoyagi, Kyota
AU - Ohno, Mitsuyo
AU - Ohmuraya, Masaki
AU - Sato, Takashi
AU - Yoshimura, Shin Ichiro
AU - Sato, Ken
AU - Harada, Reiko
AU - Kim, Yoon Jeong
AU - Osada, Hiroyuki
AU - Nemoto, Tomomi
AU - Kasai, Haruo
AU - Kitamura, Tadahiro
AU - Nagamatsu, Shinya
AU - Harada, Akihiro
N1 - Funding Information:
Acknowledgments We thank M. Takano, T. Akuzawa, K. Inami, T. Horie, Y. Okada, R. Hirai, H. Kobayashi, H. Hata, N. Atik, M. Taniguchi, A. Goto, H. Togawa, A. Watanabe, Y. Noguchi, A Koizumi, T. Saito, and K. Honda for technical assistance; D. C. Thurmond, M. Sato, T. Sobajima, M. Inoue, and T. Hara for advice; J. Miyazaki for providing the MIN6 cells; J. Mima for advice and for providing the human syntaxin1A cDNA construct; and H. Shibata for providing the GLUT4 antibody. The PlexArray HT Analyzer was lent by the Division of Innovative Research for Drug Development, Osaka University Institute for Academic Initiatives. This work was supported by Grants-in-Aid for the 21st Century Center of Excellence Program of the Japanese Ministry of Education, Culture, Sports, Science, and Technology (to K. Sato and A. Harada), Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI grants JP24390046 to A. Harada and JP26870335 to M. Kunii),the Daiwa Securities Health Foundation, the Suzuken Memorial Foundation (to T. Sato), the Daiichi Sankyo Foundation of Life Science, Novartis Foundation (Japan) for the Promotion of Science (to A. Harada), The Uehara Memorial Foundation (to S. Yoshimura), and the joint research program of the Institute for Molecular and Cellular Regulation, Gunma University.
Publisher Copyright:
© 2016 Kunii et al.
PY - 2016
Y1 - 2016
N2 - The membrane fusion of secretory granules with plasma membranes is crucial for the exocytosis of hormones and enzymes. Secretion disorders can cause various diseases such as diabetes or pancreatitis. Synaptosomal-associated protein 23 (SNAP23), a soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) molecule, is essential for secretory granule fusion in several cell lines. However, the in vivo functions of SNAP23 in endocrine and exocrine tissues remain unclear. In this study, we show opposing roles for SNAP23 in secretion in pancreatic exocrine and endocrine cells. The loss of SNAP23 in the exocrine and endocrine pancreas resulted in decreased and increased fusion of granules to the plasma membrane after stimulation, respectively. Furthermore, we identified a low molecular weight compound, MF286, that binds specifically to SNAP23 and promotes insulin secretion in mice. Our results demonstrate opposing roles for SNAP23 in the secretion mechanisms of the endocrine and exocrine pancreas and reveal that the SNAP23-binding compound MF286 may be a promising drug for diabetes treatment.
AB - The membrane fusion of secretory granules with plasma membranes is crucial for the exocytosis of hormones and enzymes. Secretion disorders can cause various diseases such as diabetes or pancreatitis. Synaptosomal-associated protein 23 (SNAP23), a soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) molecule, is essential for secretory granule fusion in several cell lines. However, the in vivo functions of SNAP23 in endocrine and exocrine tissues remain unclear. In this study, we show opposing roles for SNAP23 in secretion in pancreatic exocrine and endocrine cells. The loss of SNAP23 in the exocrine and endocrine pancreas resulted in decreased and increased fusion of granules to the plasma membrane after stimulation, respectively. Furthermore, we identified a low molecular weight compound, MF286, that binds specifically to SNAP23 and promotes insulin secretion in mice. Our results demonstrate opposing roles for SNAP23 in the secretion mechanisms of the endocrine and exocrine pancreas and reveal that the SNAP23-binding compound MF286 may be a promising drug for diabetes treatment.
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U2 - 10.1083/jcb.201604030
DO - 10.1083/jcb.201604030
M3 - Article
C2 - 27697926
AN - SCOPUS:84991235575
VL - 215
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 1
M1 - 121
ER -