ArticleThe Journal of cell biology1999
Evidence for apical endocytosis in polarized hepatic cells: phosphoinositide 3-kinase inhibitors lead to the lysosomal accumulation of resident apical plasma membrane proteins.
Article in The Journal of cell biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 66 citations in OpenAlex.
- The multifaceted significance of phosphoinositides in endocytic trafficking.FEBS letters · 2026Review
- Membrane Heterogeneity Controls Cellular Endocytic Trafficking.Frontiers in cell and developmental biology · 2020Review
- Rab17 regulates apical delivery of hepatic transcytotic vesicles.Molecular biology of the cell · 2018Article
- A Serine/Threonine Kinase 16-Based Phospho-Proteomics Screen Identifies WD Repeat Protein-1 As A Regulator Of Constitutive Secretion.Scientific reports · 2018Article
- A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells.International journal of molecular sciences · 2016Article
- Computer simulations suggest a key role of membranous nanodomains in biliary lipid secretion.PLoS computational biology · 2015Article
- Importance of endocytic pathways in liver function and disease.Comprehensive Physiology · 2014Review
- Cytokinesis defines a spatial landmark for hepatocyte polarization and apical lumen formation.Journal of cell science · 2014Article
- Bile formation and secretion.Comprehensive Physiology · 2013Review
- Vectorial entry and release of hepatitis A virus in polarized human hepatocytes.Journal of virology · 2008Article
- Recycling endosomes of polarized epithelial cells actively sort apical and basolateral cargos into separate subdomains.Molecular biology of the cell · 2007Article
- Phosphoinositide 3-kinase regulates the role of retromer in transcytosis of the polymeric immunoglobulin receptor.Experimental cell research · 2007Article
- Efficient trafficking of MDR1/P-glycoprotein to apical canalicular plasma membranes in HepG2 cells requires PKA-RIIalpha anchoring and glucosylceramide.Molecular biology of the cell · 2006Article
- Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms.PLoS biology · 2004Article
- Intracellular trafficking of bile salt export pump (ABCB11) in polarized hepatic cells: constitutive cycling between the canalicular membrane and rab11-positive endosomes.Molecular biology of the cell · 2004Article
- Nonpolarized cells selectively sort apical proteins from cell surface to a novel compartment, but lack apical retention mechanisms.Molecular biology of the cell · 2002Article
- IgG transcytosis and recycling by FcRn expressed in MDCK cells reveals ligand-induced redistribution.The EMBO journal · 2002Article
- Vps34p differentially regulates endocytosis from the apical and basolateral domains in polarized hepatic cells.The Journal of cell biology · 2001Article
- Regulation of epidermal growth factor receptor endocytosis by wortmannin through activation of Rab5 rather than inhibition of phosphatidylinositol 3-kinase.EMBO reports · 2001Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The architectural complexity of the hepatocyte canalicular surface has prevented examination of apical membrane dynamics with methods used for other epithelial cells. By adopting a pharmacological approach, we have documented for the first time the internalization of membrane proteins from the hepatic apical surface. Treatment of hepatocytes or WIF-B cells with phosphoinositide 3-kinase inhibitors, wortmannin or LY294002, led to accumulation of the apical plasma membrane proteins, 5'-nucleotidase and aminopeptidase N in lysosomal vacuoles. By monitoring the trafficking of antibody-labeled molecules, we determined that the apical proteins in vacuoles came from the apical plasma membrane. Neither newly synthesized nor transcytosing apical proteins accumulated in vacuoles. In wortmannin-treated cells, transcytosing apical proteins traversed the subapical compartment (SAC), suggesting that this intermediate in the basolateral-to-apical transcytotic pathway remained functional. Ultrastructural analysis confirmed these results. However, apically internalized proteins did not travel through SAC en route to lysosomal vacuoles, indicating that SAC is not an intermediate in the apical endocytic pathway. Basolateral membrane protein distributions did not change in treated cells, uncovering another difference in endocytosis from the two domains. Similar effects were observed in polarized MDCK cells, suggesting conserved patterns of phosphoinositide 3-kinase regulation among epithelial cells. These results confirm a long-held but unproven assumption that lysosomes are the final destination of apical membrane proteins in hepatocytes. Significantly, they also confirm our hypothesis that SAC is not an apical endosome.
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