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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.

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Department of Biological Sciences, University of Denver, Denver, CO 80210.
Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110.
Department of Biological Sciences, University of Denver, Denver, CO 80210


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.

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