HID-1 controls formation of large dense core vesicles by influencing cargo sorting and trans-Golgi network acidification
| Autor: | James A. J. Fitzpatrick, Bethany Hosford, Lan Chen, Cedric S. Asensio, Christian H. Burns, Noah F. de Leeuw, Matthew S. Joens, Blake Hummer |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Vacuolar Proton-Translocating ATPases Neuropeptide Golgi Apparatus Peptide hormone Biology PC12 Cells Exocytosis 03 medical and health sciences symbols.namesake Gene Knockout Techniques 0302 clinical medicine Animals Humans Molecular Biology Homeodomain Proteins Secretory Vesicles Peripheral membrane protein HEK 293 cells Neuropeptides Membrane Proteins Cell Biology Articles Golgi apparatus Transport protein Cell biology Rats Protein Transport 030104 developmental biology HEK293 Cells Membrane Trafficking symbols 030217 neurology & neurosurgery Biogenesis trans-Golgi Network |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | The peripheral membrane protein HID-1 localizes to the trans-Golgi network, where it contributes to the formation of large dense core vesicles of neuroendocrine cells by influencing cargo sorting and trans-Golgi network acidification. 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. |
| Databáze: | OpenAIRE |
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