HID-1 is required for homotypic fusion of immature secretory granules during maturation

  1. Wen Du
  2. Maoge Zhou
  3. Wei Zhao
  4. Dongwan Cheng
  5. Lifen Wang
  6. Jingze Lu
  7. Eli Song
  8. Wei Feng
  9. Yanhong Xue  Is a corresponding author
  10. Pingyong Xu  Is a corresponding author
  11. Tao Xu  Is a corresponding author
  1. Chinese Academy of Sciences, China
  2. 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.

Article and author information

Author details

  1. Wen Du

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Maoge Zhou

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Wei Zhao

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Dongwan Cheng

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Lifen Wang

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jingze Lu

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Eli Song

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Wei Feng

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yanhong Xue

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    For correspondence
    xueyanhong@moon.ibp.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
  10. Pingyong Xu

    College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
    For correspondence
    pyxu@ibp.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
  11. Tao Xu

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    For correspondence
    xutao@ibp.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8260-9754

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.

Reviewing Editor

  1. Kang Shen, Howard Hughes Medical Institute, Stanford University, United States

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.

Version history

  1. Received: May 24, 2016
  2. Accepted: October 17, 2016
  3. Accepted Manuscript published: October 18, 2016 (version 1)
  4. Version of Record published: November 3, 2016 (version 2)

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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  1. Wen Du
  2. Maoge Zhou
  3. Wei Zhao
  4. Dongwan Cheng
  5. Lifen Wang
  6. Jingze Lu
  7. Eli Song
  8. Wei Feng
  9. Yanhong Xue
  10. Pingyong Xu
  11. Tao Xu
(2016)
HID-1 is required for homotypic fusion of immature secretory granules during maturation
eLife 5:e18134.
https://doi.org/10.7554/eLife.18134

Share this article

https://doi.org/10.7554/eLife.18134

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