PXD007948-1

PXD007948 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-11 08:37:04	ID requested
⏵ 1	2019-01-07 08:37:29	announced

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]

curator keyword: Biological

submitter keyword: calnexin/ cholestasis/ER-stress/ NTCP/Calreticulin/xbp1/perk/lectin chaperones

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

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PRIDE project URI

• PRIDE
  1. PXD007948
     1. Label: PRIDE project
     2. Name: Calnexin depletion by ER-stress during cholestasis inhibits the Na+-taurocholate Cotransporting Polypeptide (NTCP)