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

Blake H. Hummer, Noah F. De Leeuw, Christian Burns, Lan Chen, Matthew S. Joens, Bethany Hosford, James A.J. Fitzpatrick, Cedric S. Asensio

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)3870-3880
Number of pages11
JournalMolecular biology of the cell
Volume28
Issue number26
DOIs
StatePublished - Dec 2017

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