RT Journal Article SR Electronic T1 HID-1 controls cargo sorting and dense core formation by influencing trans-Golgi network acidification in neuroendocrine cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 156794 DO 10.1101/156794 A1 Blake H. Hummer A1 Noah F. de Leeuw A1 Bethany Hosford A1 Christian Burns A1 Matthew S. Joens A1 James A.J. Fitzpatrick A1 Cedric S. Asensio YR 2017 UL http://biorxiv.org/content/early/2017/07/22/156794.abstract AB 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 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.