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Mol Biol Cell. 2017 Dec 15;28(26):3870-3880. doi: 10.1091/mbc.E17-08-0491. Epub 2017 Oct 26.

HID-1 controls formation of large dense core vesicles by influencing cargo sorting and trans-Golgi network acidification.

Author information

1
Department of Biological Sciences, University of Denver, Denver, CO 80210.
2
Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110.
3
Department of Biological Sciences, University of Denver, Denver, CO 80210 Cedric.Asensio@du.edu.

Abstract

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. They form at the trans-Golgi network (TGN), where their soluble content aggregates to form a dense core, but the mechanisms controlling biogenesis are still not completely understood. Recent studies have implicated the peripheral membrane protein HID-1 in neuropeptide sorting and insulin secretion. Using CRISPR/Cas9, we generated HID-1 KO rat neuroendocrine cells, and we show that the absence of HID-1 results in specific defects in peptide hormone and monoamine storage and regulated secretion. Loss of HID-1 causes a reduction in the number of LDCVs and affects their morphology and biochemical properties, due to impaired cargo sorting and dense core formation. HID-1 KO cells also exhibit defects in TGN acidification together with mislocalization of the Golgi-enriched vacuolar H+-ATPase subunit isoform a2. We propose that HID-1 influences early steps in LDCV formation by controlling dense core formation at the TGN.

PMID:
29074564
PMCID:
PMC5739301
DOI:
10.1091/mbc.E17-08-0491
[Indexed for MEDLINE]
Free PMC Article

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