Oncostatin M regulates membrane traffic and stimulates bile canalicular membrane biogenesis in HepG2 cells.
Hepatocytes are the major epithelial cells of the liver and they display membrane polarity: the sinusoidal membrane representing the basolateral surface, while the bile canalicular membrane is typical of the apical membrane. In polarized HepG2 cells an endosomal organelle, SAC, fulfills a prominent role in the biogenesis of the canalicular membrane, reflected by its ability to sort and redistribute apical and basolateral sphingolipids. Here we show that SAC appears to be a crucial target for a cytokine-induced signal transduction pathway, which stimulates membrane transport exiting from this compartment promoting apical membrane biogenesis. Thus, oncostatin M, an IL-6-type cytokine, stimulates membrane polarity development in HepG2 cells via the gp130 receptor unit, which activates a protein kinase A-dependent and sphingomyelin-marked membrane transport pathway from SAC to the apical membrane. To exert its signal transducing function, gp130 is recruited into detergent-resistant membrane microdomains at the basolateral membrane. These data provide a clue for a molecular mechanism that couples the biogenesis of an apical plasma membrane domain to the regulation of intracellular transport in response to an extracellular, basolaterally localized stimulus.
van der Wouden
Johanna M
JM
Department of Membrane Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands.
van IJzendoorn
Sven C D
SC
Hoekstra
Dick
D
D015703:Antigens, CD / Q000378:metabolism; D001648:Bile Canaliculi / Q000254:growth & development* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D050822:Cytokine Receptor gp130; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology
D015703:Antigens, CD; C494199:IL6ST protein, human; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D017868:Cyclic AMP-Dependent Protein Kinases