HID-1 controls formation of large dense core vesicles by influencing cargo sorting and trans-Golgi network acidification.
Mol Biol Cell
; 28(26): 3870-3880, 2017 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-29074564
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Homeodomain Proteins
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Secretory Vesicles
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Trans-Golgi Network
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Vacuolar Proton-Translocating ATPases
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Membrane Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Biol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2017
Document type:
Article