ArticleMolecular biology of the cell2006
Efficient trafficking of MDR1/P-glycoprotein to apical canalicular plasma membranes in HepG2 cells requires PKA-RIIalpha anchoring and glucosylceramide.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 66 citations in OpenAlex.
- Drug Resistance: The Role of Sphingolipid Metabolism.International journal of molecular sciences · 2025Review
- The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling.Communications biology · 2025Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators.Biology · 2021Review
- Lipid Players of Cellular Senescence.Metabolites · 2020Review
- Disruption of protein kinase A localization induces acrosomal exocytosis in capacitated mouse sperm.The Journal of biological chemistry · 2018Article
- Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling.Journal of the American Society of Nephrology : JASN · 2018Article
- Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?Cellular signalling · 2017Review
- Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters.Molecular pharmaceutics · 2017Article
- RSK1 protects P-glycoprotein/ABCB1 against ubiquitin-proteasomal degradation by downregulating the ubiquitin-conjugating enzyme E2 R1.Scientific reports · 2016Article
- Development of an oxygenation culture method for activating the liver-specific functions of HepG2 cells utilizing a collagen vitrigel membrane chamber.Cytotechnology · 2016Article
- Structural and functional hepatocyte polarity and liver disease.Journal of hepatology · 2015Review
- Extracellular galectin-3 programs multidrug resistance through Na+/K+-ATPase and P-glycoprotein signaling.Oncotarget · 2015Article
- An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes.Nature genetics · 2015Article
- The unique polarity phenotype of hepatocytes.Experimental cell research · 2014Review
- Altered lysophosphatidic acid (LPA) receptor expression during hepatic regeneration in a mouse model of partial hepatectomy.HPB : the official journal of the International Hepato Pancreato Biliary Association · 2014Article
- Protein kinase A type II-α regulatory subunit regulates the response of prostate cancer cells to taxane treatment.Cell cycle (Georgetown, Tex.) · 2014Article
- Regulation of Golgi signaling and trafficking by the KDEL receptor.Histochemistry and cell biology · 2013Review
- Cilostazol strengthens barrier integrity in brain endothelial cells.Cellular and molecular neurobiology · 2013Article
- Vesicular sorting controls the polarity of expanding membranes in the C. elegans intestine.Worm · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In hepatocytes, cAMP/PKA activity stimulates the exocytic insertion of apical proteins and lipids and the biogenesis of bile canalicular plasma membranes. Here, we show that the displacement of PKA-RIIalpha from the Golgi apparatus severely delays the trafficking of the bile canalicular protein MDR1 (P-glycoprotein), but not that of MRP2 (cMOAT), DPP IV and 5'NT, to newly formed apical surfaces. In addition, the direct trafficking of de novo synthesized glycosphingolipid analogues from the Golgi apparatus to the apical surface is inhibited. Instead, newly synthesized glucosylceramide analogues are rerouted to the basolateral surface via a vesicular pathway, from where they are subsequently endocytosed and delivered to the apical surface via transcytosis. Treatment of HepG2 cells with the glucosylceramide synthase inhibitor PDMP delays the appearance of MDR1, but not MRP2, DPP IV, and 5'NT at newly formed apical surfaces, implicating glucosylceramide synthesis as an important parameter for the efficient Golgi-to-apical surface transport of MDR1. Neither PKA-RIIalpha displacement nor PDMP inhibited (cAMP-stimulated) apical plasma membrane biogenesis per se, suggesting that other cAMP effectors may play a role in canalicular development. Taken together, our data implicate the involvement of PKA-RIIalpha anchoring in the efficient direct apical targeting of distinct proteins and glycosphingolipids to newly formed apical plasma membrane domains and suggest that rerouting of Golgi-derived glycosphingolipids may underlie the delayed Golgi-to-apical surface transport of MDR1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.