title: HID-1 is required for homotypic fusion of immature secretory granules during maturation.
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.
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Du
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Maoge
authors.initials: M
authors.lastname: Zhou
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Dongwan
authors.initials: D
authors.lastname: Cheng
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jingze
authors.initials: J
authors.lastname: Lu
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Eli
authors.initials: E
authors.lastname: Song
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.|Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Pingyong
authors.initials: P
authors.lastname: Xu
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Tao
authors.identifier: 0000-0002-8260-9754
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D055786:Gene Knockout Techniques; D018149:Glucose Intolerance; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D001678:Organelle Biogenesis; D011384:Proinsulin / Q000097:blood; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: C000624115:HID-1 protein, mouse; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D011384:Proinsulin
keywords: FIB/SEM; HID-1; biochemistry; cell biology; homotypic fusion; mouse; secretory granules maturation