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

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...

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Bibliographic Details
Published in:eLife 2016-10, Vol.5
Main Authors: Du, Wen, Zhou, Maoge, Zhao, Wei, Cheng, Dongwan, Wang, Lifen, Lu, Jingze, Song, Eli, Feng, Wei, Xue, Yanhong, Xu, Pingyong, Xu, Tao
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biophysics
Cell Biology
Data analysis
Dense core vesicles
Electron microscopy
FIB/SEM
Flow cytometry
Gene Knockout Techniques
Glucose
Glucose Intolerance
Glucose tolerance
Golgi apparatus
HID-1
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
homotypic fusion
Immunofluorescence
Insulin
Insulin-Secreting Cells - metabolism
Intolerance
Laboratories
Membrane Proteins - genetics
Membrane Proteins - metabolism
Metabolism
Mice
Microscopy
Microscopy, Electron
Microscopy, Fluorescence
Molecular modelling
Normal distribution
Organelle Biogenesis
Pancreas
Proinsulin - blood
Proteins
Rodents
secretory granules maturation
Secretory vesicles
Secretory Vesicles - metabolism
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.18134