PMID- 28125599
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20210924
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 1
DP  - 2017
TI  - N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) 
      Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus 
      Infection.
PG  - e0170419
LID - 10.1371/journal.pone.0170419 [doi]
LID - e0170419
AB  - The sodium/bile acid cotransporter NTCP was recently identified as a receptor for 
      hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein 
      trafficking or viral receptor activity is not known. NTCP contains two N-linked 
      glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to 
      a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no 
      glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan 
      supported HBV infection at a comparable level to NTCP-WT. The physiological 
      function of NTCP, the uptake of bile acids, was also not affected in cells 
      expressing these single glycosylation variants, consistent with their trafficking 
      to the plasma membrane. However, glycosylation-deficient NTCP (NTCP-N5,11Q) 
      failed to support HBV infection, showed minimal cellular expression and was 
      degraded in the lysosome. This affected the physiological bile acid transporter 
      function of NTCP-N5,11Q in a similar fashion. In conclusion, N-glycosylation is 
      required for efficient NTCP localization at the plasma membrane and subsequent 
      HBV infection and these characteristics are preserved in NTCP carrying a single 
      carbohydrate moiety.
FAU - Appelman, Monique D
AU  - Appelman MD
AD  - Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 
      Amsterdam, the Netherlands.
FAU - Chakraborty, Anindita
AU  - Chakraborty A
AD  - Institute of Virology, Technische Universitat Munchen / Helmholtz Zentrum 
      Munchen, Munchen, Germany.
AD  - Institute for Advanced Study, Technische Universitat Munchen, Munchen, Germany.
FAU - Protzer, Ulrike
AU  - Protzer U
AD  - Institute of Virology, Technische Universitat Munchen / Helmholtz Zentrum 
      Munchen, Munchen, Germany.
AD  - Institute for Advanced Study, Technische Universitat Munchen, Munchen, Germany.
FAU - McKeating, Jane A
AU  - McKeating JA
AD  - Institute for Advanced Study, Technische Universitat Munchen, Munchen, Germany.
AD  - Centre for Human Virology, University of Birmingham, Birmingham, United Kingdom.
FAU - van de Graaf, Stan F J
AU  - van de Graaf SF
AUID- ORCID: 0000-0003-4238-4359
AD  - Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 
      Amsterdam, the Netherlands.
AD  - Department of Gastroenterology and Hepatology, Academic Medical Center, 
      Amsterdam, the Netherlands.
LA  - eng
GR  - G0801976/MRC_/Medical Research Council/United Kingdom
GR  - 337479/ERC_/European Research Council/International
GR  - G1100247/MRC_/Medical Research Council/United Kingdom
GR  - MC_PC_16056/MRC_/Medical Research Council/United Kingdom
GR  - G0400802/MRC_/Medical Research Council/United Kingdom
GR  - MR/K01532X/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20170126
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Organic Anion Transporters, Sodium-Dependent)
RN  - 0 (Symporters)
RN  - 145420-23-1 (sodium-bile acid cotransporter)
SB  - IM
MH  - Glycosylation
MH  - Hep G2 Cells
MH  - Hepatitis B/*metabolism/virology
MH  - Hepatitis B virus
MH  - Humans
MH  - Mutagenesis, Site-Directed
MH  - Organic Anion Transporters, Sodium-Dependent/genetics/*metabolism
MH  - Protein Transport/physiology
MH  - Symporters/genetics/*metabolism
PMC - PMC5268470
COIS- The authors have declared that no competing interests exist.
EDAT- 2017/01/27 06:00
MHDA- 2017/08/15 06:00
PMCR- 2017/01/26
CRDT- 2017/01/27 06:00
PHST- 2016/08/25 00:00 [received]
PHST- 2017/01/04 00:00 [accepted]
PHST- 2017/01/27 06:00 [entrez]
PHST- 2017/01/27 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2017/01/26 00:00 [pmc-release]
AID - PONE-D-16-34037 [pii]
AID - 10.1371/journal.pone.0170419 [doi]
PST - epublish
SO  - PLoS One. 2017 Jan 26;12(1):e0170419. doi: 10.1371/journal.pone.0170419. 
      eCollection 2017.