HID-1 is required for homotypic fusion of immature secretory granules during maturation
- Chinese Academy of Sciences, China
- University of Chinese Academy of Sciences, China
Abstract
Secretory granules, also known as dense core vesicles, are generated at the trans-Golgi network and undergo several maturation steps, including homotypic fusion of immature secretory granules (ISGs), and processing of prehormones to yield active peptides. The molecular mechanisms governing secretory granule maturation are largely unknown. Here, we investigate a highly conserved protein named HID-1 in a mouse model. A conditional knockout of HID-1 in pancreatic β cells leads to glucose intolerance and a remarkable increase in the serum proinsulin/insulin ratio caused by defective proinsulin processing. Large volume three-dimensional electron microscopy and immunofluorescence imaging reveal that ISGs are much more abundant in the absence of HID-1. We further demonstrate that HID-1 deficiency prevented secretory granule maturation by blocking homotypic fusion of immature secretory granules. Our data identify a novel player during the early maturation of immature secretory granules.
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Author details
Funding
Ministry of Science and Technology of the People's Republic of China (2016YFA0500200)
- Tao Xu
Ministry of Science and Technology of the People's Republic of China (2013CB910103)
- Pingyong Xu
National Natural Science Foundation of China (31130065)
- Tao Xu
National Natural Science Foundation of China (31127901)
- Tao Xu
National Natural Science Foundation of China (31127002)
- Tao Xu
National Natural Science Foundation of China (31400658)
- Wen Du
National Natural Science Foundation of China (31300700)
- Dongwan Cheng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Institute of Biophysics, Chinese Academy of Sciences. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the Institute of Biophysics. All experiments were approved by the Animal Care Committee at the Institute of Biophysics (license number: SYXK2016-19). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.
Copyright
© 2016, Du et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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HID-1 is required for homotypic fusion of immature secretory granules during maturation
eLife 5:e18134.
https://doi.org/10.7554/eLife.18134
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