Opposing roles for SNAP23 in secretion in exocrine and endocrine pancreatic cells
October 3, 2016
Newly synthesized secretory proteins, such as hormones and digestive enzymes, are secreted through the fusion of secretory vesicles with the plasma membrane, which is mediated by SNARE proteins. SNAP23 is one of the SNARE proteins, and is involved in exocytotic events in diverse non-neuronal cells. However, the in vivo function of SNAP23 in the fusion of secretory granules remains largely unknown. In this study, we generated pancreatic exocrine- or endocrine-specific Snap23 knockout (KO) mice. The exocrine-specific KO mice showed decreased fusion of zymogen granules, but the endocrine-specific KO mice showed increased fusion of insulin granules and improved glucose tolerance. These results suggest that SNAP23 plays opposite roles in secretion in the exocrine and endocrine pancreas. Furthermore, we found that the SNAP23-binding compound MF286 promoted insulin secretion and improved glucose tolerance by inhibiting formation of the SNARE complex that includes SNAP23. Our study indicated that MF286 may be a candidate drug for diabetes treatment.
The Journal of Cell Biology doi:
M. Kunii, M. Ohara-Imaizumi, N. Takahashi, M. Kobayashi, R. Kawakami, Y. Kondoh, T. Shimizu, S. Simizu, B. Lin, K. Nunomura, K. Aoyagi, M. Ohno, M. Ohmuraya, T. Sato, S. Yoshimura, K. Sato, R. Harada, Y. Kim, H. Osada, T. Nemoto, H. Kasai, T. Kitamura, S. Nagamatsu, A. Harada,
"Opposingroles forSNAP23 in secretion in exocrine and endocrine pancreatic cells".
Hiroyuki Osada; Group Director
Yasumitsu Kondoh; Senior Research Scientist
Chemical Biology Research Group