ArticlePloS one2014
LKB1/AMPK and PKA control ABCB11 trafficking and polarization in hepatocytes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.Nature communications · 2026Article
- Dietary Rumen-Protected Taurine Enhances Growth Performance and Meat Quality in Heat-Stressed Crossbred Gan-Xi Goats via ModulatingFoods (Basel, Switzerland) · 2025Article
- Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.Frontiers in pharmacology · 2023Review
- Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues.NPJ Regenerative medicine · 2022Review
- In Vitro Assay System to Detect Drug-Induced Bile Acid-Dependent Cytotoxicity Using Hepatocytes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Preparation of Functional Human Hepatocytes Ex Vivo.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Collagen Sandwich Culture of Primary Hepatocytes for Image-Based Investigations.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.The Journal of cell biology · 2021Article
- SEW2871 attenuates ANIT-induced hepatotoxicity by protecting liver barrier function via sphingosine 1-phosphate receptor-1-mediated AMPK signaling pathway.Cell biology and toxicology · 2021Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.International journal of molecular sciences · 2021Review
- Bile Acid Toxicity and Protein Kinases.Advances in experimental medicine and biology · 2021Article
- LKB1 coordinates neurite remodeling to drive synapse layer emergence in the outer retina.eLife · 2020Article
- LCAT protects against Lipoprotein-X formation in a murine model of drug-induced intrahepatic cholestasis.Pharmacology research & perspectives · 2020Article
- AMP-activated protein kinase signaling regulated expression of urea cycle enzymes in response to changes in dietary protein intake.Journal of inherited metabolic disease · 2019Article
- Liver kinase B1 restoration promotes exosome secretion and motility of lung cancer cells.Oncology reports · 2018Article
- Regulation of Transporters and Channels by Membrane-Trafficking Complexes in Epithelial Cells.Cold Spring Harbor perspectives in biology · 2017Review
- Shunts, channels and lipoprotein endosomal traffic: a new model of cholesterol homeostasis in the hepatocyte.Journal of biomedical research · 2017Article
- Role of AMP-activated protein kinase α1 in 17α-ethinylestradiol-induced cholestasis in rats.Archives of toxicology · 2017Article
- Deletion of Lkb1 in adult mice results in body weight reduction and lethality.Scientific reports · 2016Article
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation.
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