PXD007948 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Calnexin depletion by ER-stress during cholestasis inhibits the Na+-taurocholate Cotransporting Polypeptide (NTCP) |
Description | Impaired bile flow (cholestasis) leads to transcriptional downregulation of the bile acid importer Na+-taurocholate co-transporting protein (NTCP) and to ER-stress in the liver. Here, we show that ER-stress induction strongly reduces NTCP protein expression, plasma membrane abundance and NTCP-mediated bile acid uptake. This is not controlled via a single specific UPR-pathway but mainly depends on the interaction of NTCP with calnexin, an ER chaperone involved in folding of N-glycosylated proteins. In mice, expression of both Ntcp and calnexin was reduced by thapsigargin-induced ER-stress. Calnexin downregulation in HepG2 and U2OS cells results in a decreased NTCP expression and a reduced bile acid uptake. Calreticulin shows partial functional redundancy with calnexin as it also interacts with NTCP, and is downregulated upon ER-stress, but specifically in calnexin-depleted cells. In conclusion, ER stress-induced downregulation of calnexin provides an additional mechanism to dampen NTCP-mediated bile acid uptake during cholestasis. |
HostingRepository | PRIDE |
AnnounceDate | 2019-01-07 |
AnnouncementXML | Submission_2019-01-07_08:37:27.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Harmjan Vos |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-10-11 08:37:04 | ID requested | |
⏵ 1 | 2019-01-07 08:37:29 | announced | |
Publication List
Robin MJD, Appelman MD, Vos HR, van Es RM, Paton JC, Paton AW, Burgering B, Fickert P, Heijmans J, van de Graaf SFJ, -Taurocholate Cotransporting Polypeptide. Hepatol Commun, 2(12):1550-1566(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: calnexin/ cholestasis/ER-stress/ NTCP/Calreticulin/xbp1/perk/lectin chaperones |
Contact List
Stan F.J van de Graaf |
contact affiliation | Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands. |
contact email | k.f.vandegraaf@amc.uva.nl |
lab head | |
Harmjan Vos |
contact affiliation | University Medical Center Utrecht Dept. Molecular Cancer Research |
contact email | h.r.vos-3@umcutrecht.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD007948
- Label: PRIDE project
- Name: Calnexin depletion by ER-stress during cholestasis inhibits the Na+-taurocholate Cotransporting Polypeptide (NTCP)