PMID- 34239896
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210710
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - Mutational Analysis of the GXXXG/A Motifs in the Human Na(+)/Taurocholate 
      Co-Transporting Polypeptide NTCP on Its Bile Acid Transport Function and 
      Hepatitis B/D Virus Receptor Function.
PG  - 699443
LID - 10.3389/fmolb.2021.699443 [doi]
LID - 699443
AB  - Homodimerization is essential for plasma membrane sorting of the liver bile acid 
      transporter NTCP and its function as Hepatitis B/D Virus (HBV/HDV) receptor. 
      However, the protein domains involved in NTCP dimerization are unknown. NTCP 
      bears two potential GXXXG/A dimerization motifs in its transmembrane domains 
      (TMDs) 2 and 7. The present study aimed to analyze the role of these GXXXG/A 
      motifs for the sorting, function, and dimerization of NTCP. The NTCP mutants 
      G(60)LXXXA(64)L (TMD2), G(233)LXXXG(237)L (TMD7) and a double mutant were 
      generated and analyzed for their interaction with wild-type NTCP using a 
      membrane-based yeast-two hybrid system (MYTH) and co-immunoprecipitation (co-IP). 
      In the MYTH system, the TMD2 and TMD7 mutants showed significantly lower 
      interaction with the wild-type NTCP. In transfected HEK293 cells, membrane 
      expression and bile acid transport activity were slightly reduced for the TMD2 
      mutant but were completely abolished for the TMD7 and the TMD2/7 mutants, while 
      co-IP experiments still showed intact protein-protein interactions. 
      Susceptibility for in vitro HBV infection in transfected HepG2 cells was reduced 
      to 50% for the TMD2 mutant, while the TMD7 mutant was not susceptible for HBV 
      infection at all. We conclude that the GXXXG/A motifs in TMD2 and even more 
      pronounced in TMD7 are important for proper folding and sorting of NTCP, and so 
      indirectly affect glycosylation, homodimerization, and bile acid transport of 
      NTCP, as well as its HBV/HDV receptor function.
CI  - Copyright (c) 2021 Palatini, Muller, Lowjaga, Noppes, Alber, Lehmann, Goldmann, 
      Glebe and Geyer.
FAU - Palatini, Massimo
AU  - Palatini M
AD  - Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus 
      Liebig University Giessen, Giessen, Germany.
FAU - Muller, Simon Franz
AU  - Muller SF
AD  - Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus 
      Liebig University Giessen, Giessen, Germany.
FAU - Lowjaga, Kira Alessandra Alicia Theresa
AU  - Lowjaga KAAT
AD  - Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus 
      Liebig University Giessen, Giessen, Germany.
FAU - Noppes, Saskia
AU  - Noppes S
AD  - Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus 
      Liebig University Giessen, Giessen, Germany.
FAU - Alber, Jorg
AU  - Alber J
AD  - Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus 
      Liebig University Giessen, Giessen, Germany.
FAU - Lehmann, Felix
AU  - Lehmann F
AD  - Institute of Medical Virology, National Reference Center for Hepatitis B and D 
      Viruses, Justus Liebig University Giessen, Giessen, Germany.
FAU - Goldmann, Nora
AU  - Goldmann N
AD  - Institute of Medical Virology, National Reference Center for Hepatitis B and D 
      Viruses, Justus Liebig University Giessen, Giessen, Germany.
FAU - Glebe, Dieter
AU  - Glebe D
AD  - Institute of Medical Virology, National Reference Center for Hepatitis B and D 
      Viruses, Justus Liebig University Giessen, Giessen, Germany.
FAU - Geyer, Joachim
AU  - Geyer J
AD  - Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus 
      Liebig University Giessen, Giessen, Germany.
LA  - eng
PT  - Journal Article
DEP - 20210622
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8257933
OTO - NOTNLM
OT  - Na+/taurocholate co-transporting polypeptide
OT  - bile acid transport
OT  - dimerization
OT  - hepatitis B virus
OT  - hepatitis D virus
OT  - protein-protein interaction
OT  - sorting
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/10 06:00
MHDA- 2021/07/10 06:01
PMCR- 2021/01/01
CRDT- 2021/07/09 07:01
PHST- 2021/04/23 00:00 [received]
PHST- 2021/06/10 00:00 [accepted]
PHST- 2021/07/09 07:01 [entrez]
PHST- 2021/07/10 06:00 [pubmed]
PHST- 2021/07/10 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 699443 [pii]
AID - 10.3389/fmolb.2021.699443 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Jun 22;8:699443. doi: 10.3389/fmolb.2021.699443. 
      eCollection 2021.